María Luisa Rodríguez-Vázquez

Acidosis and weight loss are induced by cyclosporin A in uninephrectomized rats.

Abstract The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats were assessed for 7 days and in non-nephrectomized rats for 15 days. CyA induced a marked systemic acidosis, accompanied by decreases in blood PCO2 and plasma bicarbonate. Untreated uninephrectomized rats did not show the acidosis. In CyA-treated rats the urine pH decreased (control 6.65±0.06 vs. CyA 6.18±0.08; P<0.01) as well as urinary bicarbonate (non-nephrectomized rats 7.50±1.88 mM vs. uninephrectomy plus CyA 0.75± 0.06 mM; P<0.01), suggesting partial renal compensation of systemic acidosis. Titratable acidity increased in CyA-treated rats (control 21.6±1.2 vs. CyA 63.3±12.0 µEq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not significantly altered in non-nephrectomized rats treated with CyA for 15 days. There was a striking decrease in body weight in CyA-treated rats (control 274.0±3.8 vs. CyA 225.0±5.1 g; P<0.01), but compensatory growth of the remaining kidney was not prevented by this drug or by its vehicle. In summary, CyA induced a severe metabolic acidosis in uninephrectomized rats that was not compensated by the remaining kidney, in spite of the well-preserved compensatory weight gain of this organ. Loss of body weight was significant in CyA-treated animals.

Protective effect of Ginkgo biloba extract on liver damage by a single dose of CCl 4 in male rats

Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl4; 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl4 significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 ± 1044%) and aspartate aminotransferase (AST; 6964 ± 833%), compared to control rats; CCl4 also significantly decreased serum concentration of albumin (23 ± 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 ± 33%). Furthermore, CCl 4 down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl4 produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl4: significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl4-treated rats; GbE partially prevented the increase of liver MDA (55 ± 14%) and the decrease of albumin concentration to 12 ± 0.2%. This pretreatment prevented the down-regulation of TNF-a and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl4-treated rats.

Renal failure during acute toxicity produced by tullidora ingestion (Karwinskia humboldtiana).

1. Acute effects of Karwinskia humboldtiana (Kh) were studied in some renal functions and structural patterns of renal tissue. 2. Haemodynamic changes were observed with decrements of the glomerular filtration rate, renal plasma flow and filtration fraction during acute intoxication. 3. A marked increment in the fractional excretion of sodium was observed in the rats treated with tullidora fruits (Kh). 4. Cloudy swelling and hydropic degeneration was seen 72 hr after intoxication, mainly in the proximal convoluted tubules.

The flavonoid quercetin protects and prevents against potassium dichromate-induced systemic peroxidation of lipids and diminution in renal clearance of para-aminohippuric acid and inulin in the rat.

It is well known that exposure to chromium (Cr) can lead to nephrotoxicity. Quercetin is a flavonoid of interest because of its proposed health-promoting effects. The aim of this work was to elucidate the role of quercetin against the nephrotoxicity caused by Cr in rats. Quercetin may have positive effects in combating, or helping to prevent, nephrotoxicity. It was observed that a single dose of potassium dichromate resulted in both an increase of systemic peroxidation of lipids and a decrease of the renal clearance of para-aminohippuric acid and inulin. Our results show that treatment with quercetin protected and prevented against these damaging effects.

The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a single and low dose of carbon tetrachloride in adult male rats

Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl4. Carbon tetrachloride increased the urinary concentration of total proteins, and the renal concentration of MDA; however, it did not modify the urine flux, urinary concentration of glucose, nor the inuline or the p-aminohipurate clearances. Morphologically, CCl4 generated some tubular damage that was more intense in the inner cortex of kidneys. The GbE extract counteracted the effects of CCl4 on the concentration of total proteins in urine, the concentration of renal MDA, and the renal histological changes. In conclusion the main toxic effects produced by CCl4 were prevented by the GbE, probably due to their antioxidant properties and the inhibition of the main P450 isoenzyme (CYP2E1) that metabolize CCl4.

Renal damage induced by the pesticide methyl parathion in male Wistar rats

ABSTRACT Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD50), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.

Potassium dichromate-induced changes on urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes.

It has been reported that potassium dichromate–induced nephrotoxicity is evidenced by diminution in creatinine clearance, increase in urinary protein, and structural damage to the proximal tubules. Damage to tissue often leads to the release of enzymes from the injured cells into the extracellular fluids. The aim of this study was to establish whether potassium dichromate induces changes in the urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes. Our results show that the administration of a single intraperitoneal dose of potassium dichromate decreased the activity of such enzymes in urine.