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Biomedical subjects

R Kakkar

Publications and source records attributed to R Kakkar.

At least 19 recordsLinked to original sources

Surgical management of trapezius palsy.

BACKGROUND: Injury to the spinal accessory nerve in the posterior cervical triangle leads to paralysis of the trapezius muscle. The aim of this study was to determine the indications for nerve repair or reconstructive surgery according to the etiology, the duration of the preoperative delay, and specific patient characteristics. METHODS: Of twenty-seven patients with a trapezius palsy, twenty were treated with neurolysis or surgical repair (direct or with a graft) of the spinal accessory nerve and seven were treated with the Eden-Lange muscle transfer procedure. Lymph node biopsy was the main cause of the nerve injury. The nerve repairs were performed at an average of seven months after the injury, and the reconstructive procedures were done at an average of twenty-eight months. Nerve repair was performed for iatrogenic injuries of the spinal accessory nerve, within twenty months after the onset of symptoms, and in one patient with spontaneous palsy. Reconstructive surgery was performed for cases of trapezius palsy secondary to radical neck dissection, for spontaneous palsies, and after failure of nerve repair or neurolysis. The mean follow-up period was thirty-five months. The functional outcome was assessed clinically on the basis of active shoulder abduction, pain, strength of the trapezius on manual muscle-testing, and level of subjective patient satisfaction. RESULTS: The results were good or excellent in sixteen of the twenty patients treated with nerve repair and in four of the seven patients treated with the Eden-Lange procedure. Poor results were seen in older patients and in patients with a previous radical neck dissection. CONCLUSIONS: Good results can be expected from a repair of the spinal accessory nerve if it is performed within twenty months after the injury, as the nerve is basically a purely motor nerve and the distance from the injury to the motor end plates is short. Muscle transfer should be performed in patients with spontaneous trapezius palsy, when previous nerve surgery has failed, or when the time from the injury to treatment is over twenty months. Treatment is less likely to succeed when the patient is older than fifty years of age or the palsy was due to a radical neck dissection, penetrating injury, or spontaneous palsy.

Accessory Nerve↗

Surgical management of trapezius palsy.

BACKGROUND: Injury to the spinal accessory nerve in the posterior cervical triangle leads to paralysis of the trapezius muscle. The aim of this study was to determine the indications for nerve repair or reconstructive surgery according to the etiology, the duration of the preoperative delay, and specific patient characteristics. METHODS: Of twenty-seven patients with a trapezius palsy, twenty were treated with neurolysis or surgical repair (direct or with a graft) of the spinal accessory nerve and seven were treated with the Eden-Lange muscle transfer procedure. Lymph node biopsy was the main cause of the nerve injury. The nerve repairs were performed at an average of seven months after the injury, and the reconstructive procedures were done at an average of twenty-eight months. Nerve repair was performed for iatrogenic injuries of the spinal accessory nerve, within twenty months after the onset of symptoms, and in one patient with spontaneous palsy. Reconstructive surgery was performed for cases of trapezius palsy secondary to radical neck dissection, for spontaneous palsies, and after failure of nerve repair or neurolysis. The mean follow-up period was thirty-five months. The functional outcome was assessed clinically on the basis of active shoulder abduction, pain, strength of the trapezius on manual muscle-testing, and level of subjective patient satisfaction. RESULTS: The results were good or excellent in sixteen of the twenty patients treated with nerve repair and in four of the seven patients treated with the Eden-Lange procedure. Poor results were seen in older patients and in patients with a previous radical neck dissection. CONCLUSIONS: Good results can be expected from a repair of the spinal accessory nerve if it is performed within twenty months after the injury, as the nerve is basically a purely motor nerve and the distance from the injury to the motor end plates is short. Muscle transfer should be performed in patients with spontaneous trapezius palsy, when previous nerve surgery has failed, or when the time from the injury to treatment is over twenty months. Treatment is less likely to succeed when the patient is older than fifty years of age or the palsy was due to a radical neck dissection, penetrating injury, or spontaneous palsy.

Accessory Nerve Injuries↗

Decreased expression of high-molecular-weight calmodulin-binding protein and its correlation with apoptosis in ischemia-reperfused rat heart.

A cardiac high-molecular-weight calmodulin-binding protein (HMWCaMBP) was previously identified as a homologue of the calpain inhibitor, calpastatin. In the present study, we investigated the expression of HMWCaMBP and calpains in rat heart after ischemia and reperfusion. Western blot analysis of normal rat heart extract with a polyclonal antibody raised against bovine HMWCaMBP indicated a prominent immunoreactive band of 140kDa. Both the expression and the activity of HMWCaMBP were decreased by ischemia reperfusion. Immunohistochemical studies showed strong-to-moderate HMWCaMBP immunoreactivity in normal heart and poor immunoreactivity in ischemia-reperfused heart muscle. However, the expression of micro-calpain and m-calpain in ischemia-reperfused heart was increased as compared to normal heart. The calpain inhibitory activity of ischemia-reperfused heart tissues was significantly lower as compared to normal heart tissues. The pre-ischemic and post-ischemic perfusion of hearts with a cell-permeable calpain inhibitor suppressed the increase in calpain expression but increased the HMWCaMBP expression. In-vitro HMWCaMBP was proteolyzed by micro-calpain and m-calpain. We also measured apoptosis in normal and ischemia-reperfused tissues. An increase in the number of apoptotic bodies was observed with increased duration of ischemia and reperfusion. Bcl-2 expression did not change in any of the groups, whereas Bax expression increased with ischemia-reperfusion and correlated well with the degree of apoptosis. Our findings suggest that HMWCaMBP may sequester calpains from its substrates in the normal myocardium, but it is susceptible to proteolysis by calpains during ischemia-reperfusion. Thus, decreased expression of HMWCaMBP may play an important role in myocardial injury.

Animals↗

Increased expression of N-myristoyltransferase in gallbladder carcinomas.

BACKGROUND: Activated Src, which has intrinsic protein tyrosine kinase activity, has been found in human solid tumors such as colorectal and breast carcinomas. The Src gene encodes a cytoplasmic tyrosine kinase p60src, which attaches to the inner surface of the membrane after N-terminal myristoylation and is implicated in transduction of signals to the nucleus. N-myristoyltransferase (NMT) catalyzes the biochemical modification process called N-myristoylation. To investigate whether, through Src, NMT contributes to the pathogenesis of gallbladder carcinoma, the authors investigated expression of NMT and p53 in in situ and invasive carcinomas. METHODS: One hundred cases of documented gallbladder carcinoma were reviewed, and 30 cases were selected randomly to evaluate expression of NMT and p53 by immunohistochemistry in both in situ and in invasive tumor components. RESULTS: Eighteen cases (60%) of gallbladder carcinoma showed moderate to strong cytoplasmic positivity for NMT with increased intensity in the invasive component, and 12 cases (40%) were negative. The in situ component revealed mild to moderate cytoplasmic staining in 20 cases (67%), whereas the normal gallbladder mucosa showed weak to negative cytoplasmic staining. Moderate to strong p53 staining was observed in 17 in situ cases (63%) and 24 invasive cases (80%). The in situ staining patterns of p53 were unrelated to the clinical outcome of the tumor. However, moderate to strong staining of the invasive component as observed in 15 cases (50%) was associated with a mean survival of 8.8 months. Amplification of intron-8 in normal gallbladder mucosa and invasive carcinoma were similar in intensity, suggesting the absence of NMT gene amplification in these tumors. CONCLUSIONS: The increased expression of NMT in these tumors could be due to transcriptional activation. Tumors with increased expression of NMT and p53 were associated with poor clinical outcomes as evidenced by their mean survival times. NMT is likely to play a pathogenic role in gallbladder carcinoma.

Acyltransferases↗

Altered expression of high-molecular-weight calmodulin-binding protein in human ischaemic myocardium.

A high-molecular-weight calmodulin-binding protein (HMWCaMBP) was previously identified and purified from the cytosolic fraction of bovine heart. Based on the sequence homology, amino acid analysis, antibody reactivity, and calpain inhibition, HMWCaMBP has been identified as a homologue of the calpain inhibitor calpastatin. In the present study the expression of HMWCaMBP was investigated in normal and ischaemic human myocardium. Western blot analysis of normal human cardiac muscle extract with the polyclonal antibody raised against bovine HMWCaMBP indicated a prominent immunoreactive band with a molecular mass of 140 kD. HMWCaMBP was localized in the cytoplasm and myofilaments of cardiac myocytes. Furthermore, Western blot analysis of normal and ischaemic cardiac tissues indicated a decrease in the expression of HMWCaMBP in ischaemic tissues. These studies were further substantiated by immunohistochemical studies, indicating strong to moderate HMWCaMBP immunoreactivity in normal cardiac muscle and poor to negative immunoreactivity in ischaemic muscle. The results obtained from the rat ischaemic model suggested that the expression of cardiac HMWCaMBP was significantly decreased during ischaemia/reperfusion. In addition, micro-calpain and m-calpain expression was higher in ischaemic cardiac tissue samples than in normal controls. The calpain inhibitory activity of ischaemic cardiac tissues was significantly lower than normal cardiac tissue samples. In some cases of cardiac ischaemia, HMWCaMBP highlighted the contraction band necrosis seen at the margins of a myocardial infarct. In vitro, HMWCaMBP was proteolysed by micro-calpain and m-calpain. These results indicate that HMWCaMBP could be susceptible to proteolysis by calpains during ischaemia or reperfusion and may play a contributory role in myocardial injury.

Actin Cytoskeleton↗

Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients.

The present study evaluates the presence of oxidative stress in the uncontrolled diabetic state. Glycemic control reduced the oxidative stress, but total normalization of the parameters of oxidative stress was not achieved, indicating continued oxidant injury despite optimal control of the diabetes. Vitamin E supplementation for 4 weeks in these patients further reduced the oxidative stress, suggesting that vitamin E supplementation might be helpful in reducing free-radical-induced oxidant injury.

Adult↗

N-myristoyltransferase.

Myristoylation refers to the co-translational addition of a myristoyl group to an amino-terminal glycine residue of a protein by an ubiquitously distributed enzyme myristoyl-CoA:protein N-myristoyltransferase (NMT, EC 2.3.1.97). This review describes the basic enzymology, molecular cloning and regulation of NMT activity in various pathophysiological processes such as colon cancer and diabetes.

Acyl Coenzyme A↗

Effect of glycemic control and vitamin E supplementation on total glutathione content in non-insulin-dependent diabetes mellitus.

Thirty patients with non-insulin-dependent diabetes mellitus were selected for the study. 15 age-matched healthy volunteers served as controls. Serum malonaldehyde, total glutathione, and vitamin E levels were estimated before and after glycemic control and after 4 weeks of vitamin E supplementation. Both total glutathione and vitamin E levels increased after glycemic control and showed an increase after vitamin E supplementation. Malonaldehyde levels lowered after glycemic control, but remained higher than controls. Since vitamin E supplementation significantly decreased oxidative stress in the present study, it may play a role in reducing free-radical-induced oxidant injury in diabetes mellitus.

Blood Glucose↗

Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1).

Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interactions between the cyclic nucleotide and Ca2+ second messenger systems. Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally different isozymes which exhibit distinct catalytic and regulatory properties. Some isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. These isozymes also differ in their mechanism of regulation by phosphorylation. Analysis of various regulatory reactions involving Ca2+ and cyclic adenosine monophosphate (cAMP) has revealed the importance of the time dependence of these reactions during cell activation; however, no measurement is available for the time of occurrence of specific regulatory reactions. cAMP-signalling systems provide a pivotal centre for achieving crosstalk regulation by various signalling pathways. It has been proposed that polypeptide sequences enriched in proline (P), glutamate (E), serine (S) and threonine (T), known as PEST motifs, serve as putative intramolecular signals for rapid proteolytic degradation by calpains. Calpains are Ca(2+)-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Isozyme PDE1A2 has a PEST motif and acts as a substrate for m-calpain. In this paper, we have described PDE1A2 regulation by calpains and its physiological implications. cAMP is an important component of the signal transduction pathway and plays an integral role in various physiological processes such as gene transcription, various neuronal functions, cardiac muscle contraction, vascular relaxation, cell proliferation and a host of other functions. It is important to identify the cellular processes where PDE isoform(s) and cAMP response are altered. This will lead to better understanding of the pathology of disease states and development of novel therapeutics. The different PDE1 isozymes, although similar in kinetic properties, can be distinguished by various pharmacological agents. Our recent understanding of the role of PDE1 inhibitors such as ginseng, dihydropy-ridine antagonists and antiparkinsonian agents are described in this review. The exact function of PDE1 isozymes in various pathophysiological processes is not clear because most of the studies have been carried out in vitro; therefore, it is essential that further research be directed to in vivo studies.

3',5'-Cyclic-AMP Phosphodiesterases↗

An evaluation of oxidative stress in diabetes mellitus during uncontrolled and controlled state and after vitamin E supplementation.

OBJECTIVE: The study was conducted on 50 patients (10 insulin dependent diabetes mellitus (IDDM) and 40 non-insulin dependent diabetes mellitus (NIDDM) of recently diagnosed diabetes mellitus. The main objectives of the study were: 1. To evaluate oxidative stress at uncontrolled stage. 2. To evaluate the effect of optimal control on oxidative stress irrespective of type of drug therapy used. 3. To further evaluate the effect of vitamin E supplementation on oxidative stress after achieving optimal control. This was done in order to explore anti-oxidant effect of vitamin E. METHODS: Fifty patients of uncontrolled diabetes of less than 1 year duration and without any overt complications were studied. The parameters of oxidative stress included malonyl-di-aldehyde (MDA), reduced glutathione and vitamin E levels in the blood. They were done at three stages i.e. (a) In uncontrolled stage, (b) At controlled stage and (c) After 4 weeks of vitamin E supplementation in dosage of 400 mg daily. The parameters of control included fasting blood sugar < or = 140 mg%, post prandial < or = 200 mg and HbA1c < or = 7% (analysed by prepared kit). RESULTS: The significantly raised levels of MDA and decreased levels of reduced glutathione and vitamin E during uncontrolled stage of diabetes indicated free radical stress inducing lipid peroxidation. The significant fall of MDA and rise in reduced glutathione and vitamin E levels in blood after optimal control revealed its beneficial effect on oxidative stress. The levels were not normalised but still stayed higher than controls. After 4 weeks of vitamin E supplementation, further fall in MDA and rise in reduced glutathione suggested beneficial effect of vitamin E over and above the optimal control. Vitamin E estimation in blood at this stage did not constitute parameter of oxidative stress as it was provided from outside but was done to know the compliance of patients. Normalisation or near normalisation was not achieved with vitamin E therapy indicating persistence of oxidative stress. CONCLUSION: There was an evidence of oxidative stress in diabetes which decreased with optimal control and further declined after vitamin E supplementation indicating anti-oxidant effect of vitamin E alone. Normalisation of oxidative stress was not achieved. A further study is desired to study the effect of vitamin E for longer period at least 3-6 months before a definite conclusion is drawn.

Adult↗

In vitro generation of an active calmodulin-independent phosphodiesterase from brain calmodulin-dependent phosphodiesterase (PDE1A2) by m-calpain.

In the present study we have shown that bovine brain 60-kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme (CaMPDE - PDE1A2) is proteolyzed by a Ca2+-dependent cysteine protease, m-calpain. The proteolysis of PDE1A2 by m-calpain results in its conversion to a totally calmodulin (CaM)-independent form accompanied by degradation of PDE1A2 into a 45-kDa catalytic fragment and a 15-kDa fragment. The activity of PDE1A2 is unaffected by the presence or absence of CaM during cleavage, suggesting that the interaction between CaM and PDE1A2 does not alter substrate recognition by calpain. Furthermore, we provide evidence, based on the studies of CaM overlay and phosphorylation, that the cleavage site is not present either in the CaM-binding domain or phosphorylation site. N-terminal sequence analysis of the 45-kDa fragment indicated that cleavage occurs between residues 126Gln and 127Ala, and eliminates the CaM-dependent activity of carboxy termini PDE1A2. The present findings suggest that limited proteolysis in the brain through calpains could be an alternate mechanism for activating CaMPDE(s) and for regulating intracellular levels of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗

Myristoyl-coA:protein N-myristoyltransferase from bovine cardiac muscle: molecular cloning, kinetic analysis, and in vitro proteolytic cleavage by m-calpain.

Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the attachment of myristate onto the amino terminal glycine residue of select polypeptides. Cardiac tissue expresses high levels of cAMP-dependent protein kinase whose catalytic subunit is myristoylated; however, cardiac muscle extracts were found to contain low NMT activities. Northern blot analysis of bovine heart poly(A)+ RNA probed with bovine spleen NMT cDNA revealed a 1.7-kb mRNA. Western blot analysis of cardiac muscle extracts with human NMT antibody indicated a prominent immunoreactive band with a molecular mass of 50 kDa. The expression of mRNA and protein levels in cardiac muscle is not correlated with NMT activities, suggesting the presence of regulators of the enzyme activity. We have isolated the cDNA encoding bovine cardiac muscle NMT (cNMT) by reverse transcription polymerase chain reaction. The single long open reading frame of 1248 bp of bovine cNMT specifies a protein of 416 amino acids with a predicted mass of 46,686 Da. The cDNA clone expressed in Escherichia coli resulted in the production of functionally active 50-kDa NMT. Ultrastructural and immunolocalization of NMT utilizing the immunogold labeling technique demonstrated cytoplasmic distribution with occasional mitochondrial and myofilaments localization of the NMT antibody. Cardiac muscle NMT has a higher affinity for myristoyl-CoA than toward palmitoyl-CoA. Substrate specificity indicated that cNMT has a higher affinity toward pp60src and M2 gene segment of reovirus type 3-derived peptide substrates than toward cAMP-dependent protein kinase-derived peptide. Primary translational product of cNMT sequence contained several regions rich in proline, glutamic acid, serine, and threonine, which are known as "PEST" regions. PEST-FIND analysis of the amino acid sequences indicated eight PEST regions were present in the cNMT. These PEST regions are suggested to be recognized by specific proteases, particularly Ca(2+)-dependent neutral proteases, calpains, which are responsible for the degradation of PEST-containing proteins. We have demonstrated the abolishment of NMT activity and NMT protein degradation in vitro by m-calpain. The proteolysis of cNMT by m-calpain and the abolishment of NMT activity was prevented by the calpain inhibitor, calpastatin. These observations indicate that calpains may regulate NMT activity.

Acyltransferases↗

Recombinant bovine spleen myristoyl CoA: protein N-myristoyltransferase.

Myristoyl-CoA:protein N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the co-translational transfer of myristate to the NH2-terminal glycine residue of a number of important proteins of diverse function. Recently, we have isolated full length cDNA encoding bovine spleen NMT [27] the full length cDNA was cloned and expressed in E. coli, resulting in the expression of functionally active 50 kDa NMT. Using the combination of SP-Sepharose fast flow and Mono S fast protein liquid chromatography, the enzyme was purified 20-fold with a high yield. The spleen NMT (sNMT) fusion protein exhibited an apparent molecular weight of 53 kDa on SDS-PAGE. Upon cleavage by the Enterokinase the sNMT exhibited an apparent molecular weight of 50 kDa without loss of catalytic activity. The two synthetic peptide substrates based on the N-terminal sequence of pp60src (GSSKSKMR) and cAMP dependent protein kinase (GNAAAKKRR) have different kinetic parameters of Km values of 40 and 200 microM. Recombinant sNMT was also potently inhibited by Ni2+ (histidine binder) in a concentration dependent manner with a half maximal inhibition of 280 microM. The E. coli expressed sNMT was homogenous and showed enzyme activity.

Acyltransferases↗

Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes.

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes. 2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes. 3. Male Sprague-Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals. 4. There was a significant (P < 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu-Zn-SOD activity increased (P < 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P < 0.05) in liver and pancreas. 5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern. 6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.

Animals↗

Cardiac high molecular weight calmodulin binding protein contains calpastatin activity.

A high molecular weight calmodulin binding protein (HMWCaMBP) was previously identified and purified from bovine heart cytosolic fraction [Sharma, R.K. (1990) J. Biol. Chem. 265, 1152-1157]. In this study, we report the biological function of this protein. HMWCaMBP was subjected to peptide mapping and three peptides were sequenced. Two of the three peptide sequences were shown to be highly homologous to the calpain inhibitor, calpastatin. However, the third peptide did not show homology to any known proteins. The Western blot analysis of HMWCaMBP and purified calpastatin from bovine cardiac muscle showed immunoreactivity with polyclonal antibody raised against HMWCaMBP. Furthermore, HMWCaMBP inhibited calpain II and calpain I activities in a dose dependent fashion. Our data based on sequence homology, amino acid analysis, antibody reactivity and calpain inhibition suggests that HMWCaMBP is homologous to calpastatin and may be a CaM-binding form of calpastatin.

Amino Acid Sequence↗

Amantadine: an antiparkinsonian agent inhibits bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme.

The effect of amantadine (an antiparkinsonian agent) on calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes was investigated. Amantadine inhibited bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase but not the bovine brain 63 kDa, heart and lung calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes. The inhibition of bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase was overcome by increasing the concentration of calmodulin. This suggests that amantadine may be an antagonist of calmodulin or act specifically and reversibly on the action of calmodulin. The bovine brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme is predominantly expressed in the brain and its inhibition may result in increased intracellular levels of cyclic AMP (cAMP). The increased intracellular levels of cAMP have a protective role for dopaminergic neurons. The present findings suggest that amantadine may be a valuable tool to investigate the physiological role of 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme in the progression of Parkinson's disease and gives a new insight into the action of this drug.

Amantadine↗

Antioxidant defense system in diabetic kidney: a time course study.

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)] in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.

Animals↗