Renoprotective effect of grape seeds extract in ethylene glycol induced nephrotoxic mice

Grape seed extract treatment in ethylene glycol (EG) induced nephrotoxic mice improved antioxidant status and significantly decreased urinary lactate dehydrogenase (LDH) and lipid peroxidation. The extract rendered antioxidant protection against oxidative stress induced by EG and may help in protecting renal tissue against EG toxicity.     

Dependence of the nephrotoxic effect of kanamycin on its concentration in the blood (an experimental study)]

The kinetics of changes in the urea nitrogen level of the serum was studied experimentally on narcotized cats with constant blood levels of kanamycin. A relationship between the intensity of the nephrotoxic effect of kanamycin and its blood level was found. On the basis of this relationship lower nephrotoxicity of kanamycin as compared to that of gentamicin and streptomycin under conditions of their constant blood levels was shown. However, the concentrations of gentamicin and kanamycin provided in the blood by their use in therapeutic doses differeing 3--4 times allow a conclusion that the nephrotoxic effect of kanamycin and gentamicin to be practically the same.     

Adaptation to nephrotoxic chemicals

Rats given gentamicin chronically become resistant to its nephrotoxic effects. To further explore this adaptation to nephrotoxicity, we gave male rats gentamicin 40 mg/kg/day for 12 days, then 80 mg/kg/day for 24 days. We then challenged them with 110 mg/kg/day of gentamicin for 9 days. Spermine was given 16 mg/kg/day for 42 days, then gentamicin challenge at 60 mg/kg/day for 9 days. Gossypol was given at 6 mg/kg/day for 19 days, then gentamicin at 60 mg/kg/day for 21 days. A fourth group of rats (controls) received 0.5 ml saline daily for 42 days and then received gentamicin 60 mg/kg/day for 9 days. Urine N-acetyl-beta-glucosaminidase (NAG) was measured 3 times weekly and serum creatinine was measured 5 times during the study. Each drug-treated rat increased its urine NAG from baseline values. After a period of drug administration, all NAG values returned to the predrug values. Then all animals were given gentamicin daily. NAG values increased 20-fold in the animals previously treated with saline but did not rise in the other groups. The serum creatinine frequently but not always changed in parallel with the NAG values. These observations indicate that adaptation to these nephrotoxic substances occurs and that cross-resistance to gentamicin is produced by spermine and gossypol.     

Nephrotoxins and nephrotoxic species of the genus Penicillium Link

The present article is a review about the nephrotoxic species of Penicillium Link. Some chemical and toxicological information in connection with the nephrotoxins produced is presented. Besides, different opinions about the Penicillium nephrotoxic species classification are considered; particular attention is given to the toxin produced producing species linkage. A key for the determination of the nephrotoxic Penicillium species is presented. Generally, the taxa considered in the present work have been treated in several surveys. However, some diverse opinions about its delimitation, classification and toxin production still remain.     

Age and the course of nephrotoxic nephritis in rats]

In experiments on two groups of mongrel rats (4 weeks old and 4 months old) with induced nephrotoxic nephritis it was revealed that in comparison with adult rats the course of nephritis in ratlings was characterized by lesser proteinuria, selective in nature, by lesser reducticn of endogenous creatinine clearance and diuresis. The acido- and ammo-niogenesis decreased in ratlings and adult rats to the same extent. Morphological changes in the kidneys of ratlings were less pronounced than in adult animals, and were mostly localized in the convoluted tubules. The level of DNA-synthetic activity of the epithelial nuclei of the glomeruli prevailed over this index of the convoluted tubules epithelium. The weight index of the kidneys increased less in ratlings with nephritis than in adult rats. beta-lipoproteinemia in ratlings increased 8 times. Normalization of the urine and blood indices occurred more rapidly in ratlings than in adult rats.     

Masugi's nephritis: preparation of an active nephrotoxic serum

An active nephrotoxic serum (NTS) was prepared by immunization of rabbits with isolated renal glomeruli of rats and Freund's complete adjuvant. The glomeruli were isolated from the renal cortex by the sieving procedure. Intravenous injection of the NTS to rats induced the development of marked proteinuria and the nephrotic syndrome. Histological and electron microscopic studies of renal tissue performed by days 5 and 15 since the first injection of the NTS revealed extracapillary proliferative glomerulonephritis. IgG depositions on the basal membranes of the glomerular capillaries were linear on day 5 and granular on day 15 since the first injection of the NTS.     

Evidence of renal metabolism of ifosfamide to nephrotoxic metabolites

Nephrotoxicity is a limiting factor in the use of ifosfamide in children. Despite the co-administration of uroprotective agents such as sodium 2-mercaptoethanesulfonate (mesna), ifosfamide chemotherapy is associated with nephropathy characterized by glomerular toxicity and Fanconi syndrome in many children treated with this drug. This is in distinction to cyclophosphamide, an analogue which differs solely by the position of a chloroethyl group, and which is not associated with nephrotoxicity. We hypothesized that ifosfamide is metabolized by cytochrome P450 (CYP) enzymes located in the renal tubular cell to the toxic metabolite chloroacetaldehyde; and, that the higher production of chloroacetaldehyde from ifosfamide than from cyclophosphamide explains the clinical differences in nephrotoxicity. We found that in both pig renal cortical microsomes and whole human kidney microsomes incubated with 1 mM ifosfamide for 3 hr, 2 and 3 dechloroethylifosfamide (DCEI) were produced. Our study provides evidence that porcine and human kidney microsomes are capable of biotransforming ifosfamide to DCEI metabolites that are produced in equimolar amounts with chloroacetaldehyde, indicating that chloroacetaldehyde is locally produced by renal cells as a possible mechanism for nephrotoxicity.