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Biomedical subjects

J B Hook

Publications and source records attributed to J B Hook.

At least 109 records · Page 6Linked to original sources
PubMed1982

Zinc deficiency and the kidney. II. Response of zinc-deficient rats to three diuretic drugs.

Carbonic anhydrase is a zinc metalloenzyme whose activity may be affected by zinc deficiency. This investigation was designed to evaluate the effect of zinc deficiency on the response to three diuretic drugs which vary in their capacity to inhibit carbonic anhydrase: acetazolamide, furosemide and hydrochlorothiazide. The response of the zinc-deficient rats was compared to that of pair-fed and ad libitum zinc-supplemented controls. The pattern of electrolyte excretion by zinc-deficient rats in response to the three diuretics was qualitatively similar to that of the pair-fed and zinc-supplemented rats. When corrected for differences in body weight between the three groups, the natriuretic response to the diuretics in zinc-deficient rats was greater than that of either the pair-fed or zinc-supplemented controls. Although administration of the diuretics increased potassium excretion in all groups, the response of the zinc-deficient rats was attenuated. These differences in the response of zinc-deficient rats to diuretics did not appear to be related to the capacity of these drugs to inhibit carbonic anhydrase.

Acetazolamide↗
PubMed1981

Comparative induction of xenobiotic metabolism in rodent kidney, testis and liver by commercial mixtures of polybrominated biphenyls and polychlorinated biphenyls, phenobarbital and 3-methylcholanthrene: absolute and temporal effects.

Male Fischer 344 rats were killed at various times after single or multiple treatments with polybrominated biphenyls (PBB), polychlorinated biphenyls (PCB), sodium phenobarbital (NaPB) or 3-methylcholanthrene (3MC). p-Chloro-N-methyl-aniline N-demethylase (PCNMA) and aryl hydrocarbon hydroxylase (AHH) activities were determined in the 14 000 g supernatant fraction (postmitochondrial supernate, PMS) of renal, testicular and hepatic homogenates. Cytochrome P-450 (p-450) concentrations were determined in the 100 000 g pellet fractions of the same homogenates and the effects of enzyme induction on the sensitivities of AHH in PMS to inhibition by alpha-napthoflavone (ANF) and metyrapone (MET) in vitro were determined. Single treatments with PBB or PCB induced hepatic P-450 only, while multiple treatments with PBB, PCB or 3MC induced both renal and hepatic P-450; NaPB induced only hepatic P-450, while testicular P-450 concentration was unaffected by the inducers. Treatments with PBB, PCB or 3MC shifted the Soret maxima of renal and hepatic dithionite-reduced P-450 difference spectra to shorter wavelengths. Multiple treatments with PBB, PCB or 3MC increased renal and hepatic AHH activities, but NaPB induced hepatic AHH only. Renal AHH activity was increased more rapidly than hepatic AHH after a single treatment with PBB, PCB or 3MC and returned more rapidly to control. The renal AHH induced by PBB and PCB, like that induced by 3MC, was more sensitive to inhibition by ANF in vitro than was renal AHH from naive rats. Hepatic AHH induced by PBB and PCB, unlike that induced by NaPB or 3MC, exhibited no net alterations in sensitivities to the inhibitory effects of ANF or MET. Testicular AHH activity was not induced by PBB, PCB , NaPB or 3MC. Multiple treatments with PBB, PCB or NaPB increased hepatic, but not renal or testicular PCNMA activities. The organ-specificity and time-dependency of the effects of PBB, PCB, NaPB and 3MC on P-450 concentrations and AHH activities suggest that drug metabolism in kidney, testis and liver are regulated by separate control mechanisms. It may be possible to exploit such differences in organ response to enzyme inducers as tools with which to discern the roles of local metabolism in renal and testicular chemical injury.

Animals↗
PubMed1981

Differential effect of aminoglycoside treatment on glomerular filtration and renal reabsorption of lysozyme in rats.

The aminoglycosides gentamicin, netilmicin and tobramycin were each administered (30 mg/kg/day) to male Wistar rats for 21 days. At 7, 14 and 21 days rats were anesthetized and renal clearances of inulin and egg-white lysozyme were quantified. Plasma concentration of lysozyme varied between 20 and 120 mg/liter in control and aminoglycoside treated rats. Inulin clearance (GFR) averaged 0.96 ml/min/kidney in control rats. Whereas GFR decreased to an average value of 0.47 ml/min/kidney in gentamicin treated rats, GFR did not fall in tobramycin treated rats, averaging 0.97 ml/min/kidney over the entire treatment period. In netilmicin rats GFR declined to 0.53 ml/min/kidney after 7 days of treatment and then increased to 0.78 ml/min/kidney after 14 days and 21 days of treatment. Reabsorption of lysozyme averaged about 94% of the filtered load in control rats. Reabsorption of lysozyme decreased in gentamicin treated rats to about 58% after 7 days and 14 days of treatment and increased to 79% after 21 days of treatment. After tobramycin reabsorption of lysozyme decreased to about 67% after 7 days of treatment and increased to 85% after 14 days and 21 days of treatment. Reabsorption of lysozyme remained unchanged when compared to controls over the entire treatment period in netilmicin treated rats. Thus, gentamicin reduced both GFR and renal reabsorption of lysozyme. Netilmicin reduced GFR somewhat without altering lysozyme reabsorption whereas tobramycin compromised lysozyme reabsorption without altering GFR. These differences might suggest differences in site(s) of action of various aminoglycosides.

Absorption↗
PubMed1981

Induction of drug-metabolizing enzymes and toxicity of trans-stilbene oxide in rat liver and kidney.

The effect of trans-stilbene oxide (TSO) on organ function and morphology and on drug-metabolizing enzymes was determined in male Sprague-Dawley rats. TSO (300 or 600 mg/kg) was administered i.p., once daily for 5 consecutive days. At a dose of 3400 mg/kg, TSO did no alter body weight, but increased liver weight. The higher dose (600 mg/kg) markedly decreased body weight. TSO treatment (300 mg/kg) induced several drug-metabolizing enzymes. Epoxide hydrolase activity was enhanced in the liver, kidney and lung. In contrast, arylhydrocarbon hydroxylase activity was not significantly altered. Glutathione S-transferase activity, with 1-chloro-2,4-dinitrobenzene as substrate, and uridine diphosphoglucuronyl transferase activity, with p-nitrophenol as substrate, were also increased in the liver and kidney after TSO treatment. It appears that TSO induces hepatic and renal enzyme activities in a similar manner. Treatment with the higher dose of TSO depressed accumulation of p-amino-hippurate by renal cortical slices and increased blood urea nitrogen concentration. Histological examination of kidney sections after treatment with TSO revealed no abnormality. The lower dose led to negligible alteration in liver and the higher dose resulted in mild to moderate hepatic cellular.

Animals↗
PubMed1981

Acute nephrotoxicities and hepatotoxicities of 1,2-dibromo-3-chloropropane and 1,2-dibromoethane in male and female F344 rats.

Four consecutive intraperitoneal (i.p.) injections with 40 mg/kg of 1,2-dibromo-3-chloropropane (DBCP) reduced the in vitro accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) by slices of renal cortex and increased blood urea nitrogen (BUN) concentration in both male and female rats, but elevated serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in females only. Four consecutive treatments with 1,2-dibromoethane (EDB) reduced the accumulation of PAH in male rats, but failed to alter TEA accumulation, BUN concentration or GPT and GOT activities in rats of either sex. Single i.p. injections of EDB or DBCP (40 mg/kg, approximately one-half of the acute, i.p. LD50 values) were without effect on serum GPT and GOT activities, BUN concentration or the accumulations of PAH and TEA in male rats when measured 24, 48 or 96 h after treatment, except that PAH accumulation was reduced at 96 h. These results indicate that BUN and the accumulations in vitro of PAH and TEA by renal cortical slices are appropriate endpoints for studying DBCP nephrotoxicity. Measurements of serum GOT and GPT activities detected DBCP hepatotoxicity in female rats only. The nephrotoxicity of EDB was indicated by measurement of TEA accumulation only.

Alanine Transaminase↗
PubMed1981

Effect of acetazolamide on renal function of the newborn piglet.

The effects of renal development on the response of newborns to acetazolamide were determined in an animal model, 5- and 20-day-old piglets. Increasing doses of acetazolamide increased both sodium and potassium excretion in 5-day-old piglets. Sodium excretion increased from 1.89 muEq/min during control periods to 15.7 muEq/min during infusion of acetazolamide (75 mg/kg/h). Potassium excretion increased to 20 muEq/min during acetazolamide infusion and urine pH increased from 5.7 to over 8.0. Sodium excretion by 20-day-old piglets given acetazolamide was similar to that of 5-day-old piglets but potassium excretion was twice as great (40 muEq/min). Changes in urine pH of the two groups were identical. It is concluded that the natriuretic response of 5-day-old piglets to acetazolamide is similar to that of older animals. In newborn piglets, moderate increases in sodium excretion by acetazolamide were accompanied by a marked kaliuresis. These data may identify a role for carbonic anhydrase in potassium excretion by newborn similar to that of adults.

Acetazolamide↗