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Biomedical subjects

M F Khan

Publications and source records attributed to M F Khan.

At least 19 recordsLinked to original sources
PubMed2004

Transarterial chemoembolization alone and in combination with other therapies: a comparative study in an animal HCC model.

The purpose of this study is to compare transarterial chemoembolization (TACE) alone and in combination with other therapies in an animal model. Subcapsular implantation of a solid Morris hepatoma 3924A in the liver was carried out in 50 male ACI rats (day 0). Tumor volume (V1) was measured by MRI (day 13). After laparotomy and retrograde placement of a catheter into the gastroduodenal artery (day 14), the following protocols of the interventional procedure were applied: TACE (mitomycin C + lipiodol) + immunotherapy (group A: TNFalpha + IL-2, group B: OK-432 + IL-2); TACE + antiangiogenesis therapy (group C: TNP-470, group D: endostatin); TACE alone in group E (control group). Tumor volume (V2) was assessed by MRI and the mean ratio of x (V2/V1) was calculated. Data were analyzed using Dunnett's t test (comparing therapeutic groups with the control group) and the Student-Newman-Keuls test (comparing significant therapeutic groups). Multivariate analysis showed a significant reduction in the tumor growth rate (P<0.05) in groups B (x=6.53) and C (x=4.01) compared to the mean ratio of the control group E (x=9.14). Significant results were observed in group C (P<0.05) in comparison with the other therapeutic groups. TACE combined with immunotherapy (OK-432) and antiangiogenesis therapy (TNP-470) retards tumor growth compared with TACE alone in an HCC animal model.

Angiogenesis Inhibitors↗
PubMed2003

First report on sequential totally endoscopic thymomectomy and adrenalectomy using computer-enhanced telemanipulation.

BACKGROUND: Laparoscopic adrenalectomy is considered the standard method for removal of benign adrenal tumors, regardless of hormone activity. Minimally invasive surgery for thymomectomy aims at limited approaches, avoiding complete sternotomy or large thoracotomy. METHODS: We report on a case in which totally endoscopic thymomectomy and adrenal gland resection were performed sequentially using a computer-enhanced telemanipulation system within 3 weeks. RESULTS: Operating time was 4.5 h for totally endoscopic adrenalectomy and 1.5 h for totally endoscopic thymomectomy. The patient was transferred to the normal ward on the day of operation after either procedure and had an uneventful recovery. Pathology yielded no malignancy in both cases. CONCLUSION: This report demonstrates the safety and feasibility of various totally endoscopic procedures performed sequentially.

Adenoma↗
PubMed2003

Operative techniques in awake coronary artery bypass grafting.

BACKGROUND: Off-pump coronary artery bypass grafting was implemented to reduce trauma of surgical coronary revascularization by avoiding extracorporeal circulation. High thoracic epidural anesthesia further reduces intraoperative stress and postoperative pain. In addition, this technique even allows awake coronary artery bypass grafting, avoiding the drawbacks of mechanical ventilation and general anesthesia in high-risk patients. METHODS: Thirty-four patients underwent awake coronary artery bypass grafting with left internal thoracic artery to left anterior descending coronary artery by partial lower ministernotomy (n = 20), H-graft technique (n = 2), or rib cage-lifting technique (n = 2). In 9 cases we performed double bypass grafting, and in 1 case we performed triple-vessel coronary artery revascularization through complete median sternotomy. In addition to clinical outcomes, visual analog scale pain scores were recorded on days 1, 2, and 3 after surgery. RESULTS: Thirty-one patients remained awake throughout the whole procedure. Three patients required secondary intubation because of incomplete analgesia (n = 1) or pneumothorax (n = 2). Procedure time was 90 +/- 31 minutes, and recovery room stay was 4.2 +/- 0.6 hours. There were no in-hospital deaths or serious postoperative complications. In 1 case a graft occlusion was documented on predischarge angiography. Early postoperative pain was low (visual analog scale score of 30 +/- 6). CONCLUSION: These data demonstrate the feasibility and safety of various surgical coronary revascularization techniques without general anesthesia. Continuation of thoracic epidural analgesia provides good pain control and fast mobilization postoperatively. Surprisingly, the awake coronary artery bypass grafting procedure was well accepted by the patients.

Aged↗
PubMed2002

[Total arterial bypass operations with complete sternotomy in the awake patient].

BACKGROUND: In minimally invasive coronary artery bypass surgery beating heart procedures and operations via limited incisions became more popular and are routinely performed in many centers. An additional approach to minimize general trauma is avoidance of general anesthesia endotracheal intubation. PATIENTS AND METHODS: Between March and June 2001, 14 spontaneously breathing patients underwent coronary artery bypass grafting on the beating heart without general anesthesia. Intra- and postoperative analgesia management was performed using continuous epidural infusion of local anesthetics at level Th2-Th3. Single (n = 8) as well as double (n = 5) and triple (n = 1) bypass grafting was performed with the off pump technique. Surgical access to the chest cavity was created via partial (n = 8) or complete sternotomy (n = 6). RESULTS: Twelve patients remained awake throughout the procedure; 2 patients required secondary intubation due to incomplete sensory block and pneumothorax. Operating time was 94 +/- 18 minutes. Intermediate care monitoring time amounted to 4.8 +/- 0.6 hours. No surgery-related complications or myocardial infarction occurred. Postoperative angiography reviewed good graft function in all patients. CONCLUSION: Our preliminary experience shows that complete surgical revascularization is safe and feasible without endotracheal intubation and general anesthesia. Thus, invasiveness in cardiac surgery is further reduced with less need for intensive care unit monitoring enabling faster mobilization and recovery.

Aged↗
PubMed2002

Computer-enhanced telemanipulation enables a variety of totally endoscopic cardiac procedures.

BACKGROUND: Since its introduction in the field of cardiac surgery in 1997, computer-enhanced telemanipulation has been used in a number of different specialized areas. In cardiac surgery, various procedures have been successfully completed in totally endoscopic fashion ever since. Between June 1999 and January 2002, 75 closed-chest cardiac procedures have been performed at our institution using the da Vinci telemanipulation system. PATIENTS AND METHODS: In 42 patients, a single-vessel totally endoscopic coronary artery bypass was performed on the arrested heart (left internal thoracic artery (LITA) to left anterior descending artery (LAD), n = 36; right internal thoracic artery (RITA) to right coronary artery (RCA), n = 6). 12 patients had different types of multivessel revascularization using both internal thoracic arteries. 8 patients underwent LITA-to-LAD grafting on the beating heart. 10 patients underwent closure of an atrial septal defect (9 direct, 1 patch). 3 patients received an epicardial left ventricular pacemaker lead, 2 of which were reoperations. RESULTS: Overall conversion rate to any kind of incision was 25 %. The last 26 LITA to LAD patients on the arrested heart had a conversion rate of 4 %. There were no mortalities, 3 patients required reexploration via a median sternotomy, and one patient suffered a hypoxemic brain damage. The first 22 TECAB patients demonstrated excellent graft patency in angiographic control upon discharge. None of the atrial septal defect (ASD) closures showed any residual shunt on the intraoperative transesophageal echocardiogram (TEE). Patients with end-stage heart failure had successful biventricular stimulation. CONCLUSION: Our current experience confirms the feasibility of various totally endoscopic cardiac procedures with good clinical outcomes. After a steep learning curve, the conversion rate could be lowered to an acceptable figure. Some of these procedures at our institution became a reasonable treatment alternative in selected patients.

Coronary Artery Bypass↗
PubMed2001

Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice.

Tetrachloroethene (PCE), a common industrial solvent and environmental contaminant, is primarily used in the dry-cleaning industry. The toxicity of PCE has been linked to vision disorders, renal and hepatic cancer, and autoimmune diseases. Although the mechanism of toxicity is not fully understood, PCE forms trichloroacylated protein adducts in tissues where toxicity is known to occur. These adducts may be responsible for toxicity by altering the function of cellular proteins. Using Western blot analysis, formation of trichloroacylated protein adducts has been reported. To determine the localization of the adducts in a specific zone of a tissue, immunohistochemical staining was used in the study. An antiserum to trichloroacylated proteins was raised in rabbits and its specificity was established by enzyme-linked immunosorbent assay (ELISA). Female MRL-lpr/lpr and MRL +/+ mice were treated with PCE using a single 5-mmol/kg dose over 24 h or on every fourth day for 6 wk (total 20 doses). Formation of trichloroacylated protein adducts was observed in the liver, and localized to the centrilobular zones. Intensity and circumference of the staining around the central vein were much greater in subchronically treated mice than in acutely treated mice. No immunochemical reactivity was observed in any of the other tissues examined. This study shows that hepatic trichloroacylated protein adducts are localized in a region of the liver where PCE-mediated toxicity is known to occur. Immunohistochemical localization of these adducts and its association with PCE-induced toxicity support the contention that adducts may contribute to toxicity.

Acylation↗
PubMed2001

Anti-malondialdehyde antibodies in MRL+/+ mice treated with trichloroethene and dichloroacetyl chloride: possible role of lipid peroxidation in autoimmunity.

Trichloroethene (TCE) and one of its metabolites dichloroacetyl chloride (DCAC) are known to induce/accelerate autoimmune (AI) response in MRL+/+ mice as evident from anti-nuclear, anti-ssDNA, anti-cardiolipin, and DCAC-specific antibodies in the serum (Khan et al., Toxicol. Appl. Pharmacol. 134, 155-160, 1995). In the present study, we measured anti-malondialdehyde antibodies (AMDA) in the serum of TCE- or DCAC-treated mice in order to understand the contribution of lipid peroxidation to this AI response. Female MRL+/+ mice (5 weeks old) received ip injections of 10 mmol/kg TCE or 0.2 mmol/kg of DCAC in corn oil (100 microl) every 4(th) day for 6 weeks, while controls received an equal volume of vehicle only, and AMDA was measured in the sera of these animals by an ELISA established in our laboratory. While TCE treatment caused only marginal induction of AMDA, DCAC treatment elicited a significant AMDA response. Furthermore, a time-response study of DCAC (0.2 mmol/kg, every 4(th) day, for 2, 4, 6, or 8 weeks) showed an induction of AMDA (3/4) after 4 weeks of treatment, which was even greater at both 6 and 8 weeks of DCAC treatment (5/5). These findings were further substantiated by the presence of AMDA in systemic lupus erythematosus-prone MRL-lpr/lpr mice as early as 6 weeks of age. Presence of AMDA, as observed in this study, not only indicates increased lipid peroxidation (oxidative stress), but also suggests a putative role of oxidative stress in inflammatory autoimmune diseases.

Acetates↗
PubMed2001

Amyloidosis.

Amyloidosis is not a single disease but a series of diseases in which there is extracellular deposition of a protein which, although it may be derived from different and unrelated sources, folds into a beta pleated sheet. There have recently been significant advances in elucidating the pathogenesis and in the treatment of this group of disorders. By identifying the source of precursor protein, treatment is aimed at eliminating or reducing the extent of deposition and is tailored for each patient. Early diagnosis is required for the optimal effect of treatment on patient survival and quality of life. An increased awareness among physicians of the spectrum of the disease and tools to aid its diagnosis is of increasing importance.

Amyloidosis↗
PubMed2000

Contribution of nitrosobenzene to splenic toxicity of aniline.

To elucidate the mechanism(s) of splenic toxicity of aniline, studies were conducted with nitrosobenzene (NB), an N-oxidized metabolite of aniline. Male Sprague-Dawley rats were given 0.025, 0.05, 0.1, or 0.2 mmol/kg/d of NB in 0.5 ml of 0.25% agar by gavage for 4 d; control rats received the vehicle only. Animals were euthanized at 24 h following the last dose. NB treatment resulted in decreased erythrocyte counts, whereas methemoglobin content increased at 0.1- and 0.2-mmol/kg doses. Spleen weight to body weight ratios were greater by 55 and 81% at O.1- and 0.2-mmol/kg NB doses, respectively. Total iron content in the spleens of NB-treated rats showed dose-dependent significant increases, and the nonheme iron followed a similar pattern. Splenic lipid peroxidation showed a dose-dependent response and was greater by 19, 56, 74, and 85% at the 4 doses, respectively. Malondialdehyde (MDA)-protein adducts, as quantitated by a competitive enzyme-linked immunosorbent assay (ELISA), were markedly greater in all the NB-treated groups, with the highest increase of 248% at 0.2 mmol/kg. Furthermore, NB exposure also resulted in greater protein oxidation (carbonyl content) in the spleens at 0.1- and 0.2-mmol/kg doses. These results suggest that NB is a splenotoxin and therefore can contribute to the splenic toxicity of aniline. Results of this study further support our earlier findings that oxidative stress is a potential mechanism in the splenotoxicity of aniline.

Aniline Compounds↗
PubMed1999

Multivisceral transplantation for megacystis microcolon intestinal hypoperistalsis syndrome.

BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare autosomal recessive disorder causing a functional neonatal bowel obstruction. Its etiopathogenesis is not fully understood. The prognosis is poor in the majority of cases; most patients die before the age of 6 months. In this report, we describe our experience with three patients with MMIHS in whom multivisceral transplantation was performed. METHODS: Three patients with MMIHS underwent multivisceral transplantation. All patients were females with a history of long-term total parenteral nutrition (TPN) with TPN-related cholestatic liver disease. RESULTS: Patient 1 died 17 months after transplantation because of aspiration after revision of her feeding gastrostomy. At the time of death, the graft was functioning and the patient was completely off TPN. Patient 2 is alive 17 months after transplant. She is a fully functional, active 2-year-old and has also recently begun oral feeding after intensive rehabilitation. Patient 3 died on day 44 of multisystem failure. CONCLUSIONS: This is the first report in the literature of multivisceral transplantation for MMIHS. Although one of the three patients died 44 days after surgery from multiorgan system failure, the other two patients had long-term survival after transplant and both grew well on enteral feeding alone. One patient died 17 months from a non-transplant-related complication, while the other is living at home off of TPN, with almost complete dietary rehabilitation 17 months after transplant. Our case reports suggest that multivisceral transplantation is a valuable therapeutic option for patients affected by MMIHS with TPN-induced liver failure.

Abnormalities, Multiple↗
PubMed1999

Iron exacerbates aniline-associated splenic toxicity.

Our earlier studies have shown that aniline exposure in rats causes time- and dose-dependent accumulation of iron in the spleen, which may exacerbate aniline splenotoxicity by catalyzing free-radical reactions. The present studies were conducted to test whether aniline-induced splenic toxicity could be potentiated by iron overload. For 30 d male Sprague-Dawley rats received the following treatments: 0.5 mmol/kg/d aniline hydrochloride (AH) by gavage (AH group); 3% carbonyl iron-supplemented diet (IR group); 0.5 mmol/kg/d AH by gavage and iron-supplemented diet (AH + IR group); or no treatments (controls). Treatment-related significant increases in total iron, low molecular weight chelatable iron, lipid peroxidation, and protein oxidation were observed in the spleens of all the groups compared to control. However, these changes were much greater in the combined AH + IR group. The aniline-induced morphological changes in the spleen were consistent with our earlier observations, but were more pronounced in the AH + IR group. The increased toxicity, as evident from greater oxidative stress and morphological changes in the AH + IR group, suggests that iron potentiates the splenic toxicity of aniline.

Aniline Compounds↗
PubMed1999

Thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.

Adolescent↗
PubMed1999

Fatty acid anilides: in vivo formation and relevance to toxic oil syndrome.

Toxic oil syndrome (TOS), a multisystemic epidemic outbreak in 1981 in Spain, was caused by the ingestion of a cooking oil mixture containing rapeseed oil denatured with aniline. The mechanisms and causative agents responsible for the TOS are still not known. Although primary lesions observed in TOS patients could not be reproduced experimentally, the levels of fatty acid anilides (FAAs) and aniline in TOS-related cooking oil were considered proximate markers of TOS. Aniline, available from free aniline and FAAs ingested with TOS-related cooking oil, and its reconjugation with endogenous fatty acids could be an early event leading to TOS. Therefore, the present study was undertaken to determine the formation of FAAs following an oral dose of 2 mmol/kg aniline hydrochloride (AH) via gavage in rats. Here, 16:0, 18:0, 18:1, 18:2, 18:3, and 20:4 FAAs were analyzed in the whole blood, brown fat, liver, and pancreas at 0 (control), 0.25, 0.5, 1, 3, 6, 12, 24, and 48 hours. Generally, 16:0 and 18:1 FAAs were detected in the whole blood, brown fat, and liver of AH-treated rats with highest mean levels at 0.25 or 0.5 hour, except 3 hours for the whole blood. Only 16:0 FAA was detectable in the pancreas of AH-treated animals. The 18:0 FAA was also detected frequently in the liver while other FAAs were either in trace amounts or not detectable in the tissues analyzed in the present study. Overall, highest formation of the 16:0 FAA was found in the liver followed by pancreas and of 18:1 FAA in the whole blood and brown fat. These results indicate a rapid formation and further metabolism and disposition of FAAs in rat model and support our previous findings that 18:1 and 16:0 fatty acids are better substrates for the conjugation with aniline. Surprisingly, a small or trace amount of a few FAAs also detected in the tissues of control rats indicates their endogenous biosynthesis and/or presence. Results of 18:1 fatty acid incubation and aniline in the presence of fatty acid ethyl ester synthase, purified to homogeneity from rat liver microsome, suggest that formation of FAAs is catalyzed by an enzyme involved in the conjugation of fatty acids with xenobiotic alcohols. Because the FAAs are known to exert a wide range of toxicity in experimental animals and primary cell cultures, in vivo formation of FAAs could be an early event leading to TOS.

Anilides↗
PubMed1999

Oxidative modification of lipids and proteins in aniline-induced splenic toxicity.

Our earlier studies with aniline suggested the involvement of oxidative stress as an early toxic event in the spleen. In order to understand the status and consequences of the damaging oxidative reactions, especially during the progression of characteristic splenic lesions, time-dependent subchronic studies were conducted in rats. Male Sprague-Dawley rats were treated with 65 mg/kg/day aniline in the drinking water, while control rats received drinking water only. The animals were euthanized after 1, 2, or 3 months of aniline exposure. Total iron content was remarkably greater in the aniline-treated rats than in age-matched controls. There were time-dependent increases in splenic lipid peroxidation of aniline-treated rats. Malondialdehyde-protein adducts were quantitated by a competitive ELISA and showed greater concentrations in the spleens of aniline-treated rats, further substantiating our lipid peroxidation results. Protein oxidation in the spleens of aniline-treated rats was also greater, with a maximum increase of approximately 76% at 3 months. Western blot analysis for oxidized proteins showed two distinct protein bands at approximately 114 kD and approximately 69 kD in both post-nuclear and mitochondrial fractions of the spleens. Furthermore, densitometric analysis of the blot showed increased band intensities of the oxidized proteins in both these spleen fractions from aniline-treated rats, suggesting the susceptibility of these proteins to aniline-induced oxidative stress. The most prominent morphological changes in the spleens of aniline-treated rats included thickening of the capsule, and capsular cells with nuclear prominence and hyperchromia indicative of capsular hyperplasia. These capsular changes and fibrosis of capsule, splenic trabeculae, and red pulp were noted at all three time points after aniline exposure. Our studies thus suggest that aniline-induced oxidative stress in the spleen is an ongoing event that leads to oxidative modifications of biomolecules. Such oxidative modifications, directly or indirectly, could contribute to the splenic toxicity leading to deleterious consequences, including capsular hyperplasia and fibrosis, as observed in this study, and possibly tumorigenesis in chronic aniline exposure conditions.

Aniline Compounds↗
PubMed1998

Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.

BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.

Adult↗
PubMed1998

Phenylhydroxylamine: role in aniline-associated splenic oxidative stress and induction of subendocardial necrosis.

To elucidate the role of N-phenylhydroxylamine (PHA, N-hydroxylated metabolite of aniline) in the selective toxicity of aniline to the spleen, dose-dependent studies were conducted with PHA in rats. Male Sprague-Dawley rats were given four doses each (1 dose/day) of 0.025, 0.05, 0.1, or 0.2 mmol/kg PHA in 0.5 ml of aqueous agar (0.25%) by gavage. The control animals received an equal volume of vehicle only. The animals were euthanized 24 h following the last dose. PHA toxicity in the blood was evident from a dose-dependent increase of methemoglobin. The most affected organ was spleen, which appeared dark and enlarged (splenomegaly) and showed increased spleen-to-body weight ratios, which were 28, 40, 66, and 87% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. Splenic lipid peroxidation (malondialdehyde content) was higher in all PHA-treated groups, whereas splenic protein oxidation (carbonyl content) increased in only the 0.05, 0.1, and 0.2 mmol/kg groups. The total iron content in the spleen also showed increases of 88, 135, 168, and 209% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. These biochemical changes were accompanied by a dose-dependent vascular congestion in the spleen, a characteristic feature of aniline toxicity. Although the ratio of organ to body weight increased for both testes and heart at the highest dose, striking morphological changes were observed only in heart. The cardiac lesions consisted of a both acute and resolving multifocal subendocardial necrosis involving predominently the left ventricle. Our results suggest that PHA is a splenotoxin and thus contributes to the toxicity of aniline, while at a high dose, it is also cardiotoxic, perhaps due to anoxia associated with the marked methemoglobinemia. These results further support the involvement of oxidative stress in the splenotoxicity of aniline which may be caused by its reactive metabolite(s) such as PHA.

Aniline Compounds↗