Optimal dosage and early intervention of L-ascorbic acid inhibiting K2Cr2O7-induced renal tubular cell damage.

Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 µg/mL. Supplementation of L-ascorbic acid with 30 µg/mL and within 8 h of chromium intoxication (K2Cr2O7, Cr6+) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy. Intracellular chromium concentrations were estimated using electrothermal atomic absorption spectrometry. Treatment of L-ascorbic acid within 8 h of chromium intoxication significantly decreased the entry of chromium into the cells. Moreover, concomitant administration of L-ascorbic acid with repeatedly dosing at 8-hourly intervals had a better protective effect at lower concentration of L-ascorbic acid when compared to single dosing of L-ascorbic acid at an early time point of chromium intoxication. These findings might help physicians develop effective therapy strategies in renal failure.

Chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract against chromium-induced testicular toxicity in rats.

This study was conducted to determine the mechanism underlying the chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract (MOLEE) against chromium-induced impairments of rat testes using biochemical methods. Twenty male Wistar rats were divided into four groups of five animals each. Group I (control), group II injected potassium dichromate (8 mg kg(-1) ) i.p., group III gastrogavaged MOLEE (500 mg kg(-1) ) p.o. and group IV received (potassium dichromate plus MOLEE) by the same doses for 60 days. After the blood samples were collected, the animals were sacrificed to determine the testicular antioxidant status and sperm parameters. The chromium-treated group exhibited a significant decrease in testicular antioxidant enzymatic activities, local immunity and sperm parameters as well as an increase in inflammatory markers when compared with the control and MOLEE-treated group. However, concurrent administration of chromium and MOLEE significantly ameliorated the chromium effects on the sperm parameters, local immunity, inflammatory markers and antioxidant enzymatic activities compared with rats exposed to chromium alone. This study concludes that chronic exposure to chromium produces clear testicular toxicity, which can either be prevented or at least decreased by concomitant administration of MOLEE. Interestingly, the metal ion chelation could attribute partly the antioxidant activities of MOLEE.

Protective effect of ginger against toxicity induced by chromate in rats.

The evaluation of the effect of ginger on the modulation of toxic effects induced by chromate is the objective of our study. 50 male rats Albinos Wistar were divided to five groups as follow: group I (T) is served as control, received a mineral water by gavage (per os); group II (G) received an experimental diet with 2% of ginger; group III (Cr) received an oral dose of potassium dichromate (15 mg/kg) and normal diet; group IV (CrG): received an oral dose of potassium dichromate (15 mg/kg) and an experimental diet containing 2% ginger; and group V (Cr(+)G) received an oral dose of potassium dichromate (25 mg/kg) and an experimental diet with 2% of ginger. The results of this study indicate that the chromate provoked a haematoxic effect (anemia), nephrotoxic, hepatotoxic, and also a perturbation in lipids profile. In addition, chromate has a pro-oxidant effect, which was indicated by decrease of reduced glutathione (GSH) levels in different tissues. However, the administration of ginger revealed a reduction of the intensity of oxidative stress induced by the chromate resulting in the decrease of the majority of the previous parameters concentrations. In conclusion we demonstrated that ginger has potent antioxidants activity, revealed by the amelioration of chromate's toxic effects. We can say that ginger has a protective effect towards damages induced by the chromate.

Protective effects of Selenium (Se) on Chromium (VI) induced nephrotoxicity in adult rats.

Chromium is a toxic metal implicated in human diseases. This study was focused on investigating the possible protective effect of Se against K(2)Cr(2)O(7). Female Wistar rats, used in this study, were divided into four groups of six animals each: group I served as control which received standard diet; group II received orally only K(2)Cr(2)O(7) (700 ppm equivalent to 67 mg/kgbw); group III received both K(2)Cr(2)O(7) and Se (0.5 mg/kg of diet); group IV received Se (0.5mg Na(2)SeO(3)/kg of diet). The exposure of rats to K(2)Cr(2)O(7) for 21 days provoked renal damages with a significant increase in kidney malondialdehyde, superoxide dismutase, plasma creatinine, and uric acid levels, while catalase, glutathione peroxidase, non-protein thiol, Metallothionein and plasma urea levels decreased. Coadministration of Se in the diet of chromium-treated group improved malondialdehyde, renal biomarkers levels and antioxidant enzyme activities. Kidney histological studies confirmed biochemical parameters and the beneficial role of selenium.

Pycnogenol prevents potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. Recent evidence indicates that Pycnogenol (PYC), French maritime pine bark extract, exhibits antioxidant potential and protects against various oxidative stressors. The aim of the present study was to examine the modulating impacts of PYC on potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats. Male Wistar rats were divided into four groups. The first group was control, the second group was control plus pre-treated with PYC (10 mg/kg, body weight; in saline; intraperitoneally; once daily for 3 weeks) as drug control and the third group was saline pre-treated plus treated with a single injection of K2Cr2O7 (15 mg/kg, body weight; in saline; intraperitoneally) as toxicant group. The fourth group was PYC pre-treated plus K2Cr2O7 injected. Forty-eight hours after K2Cr2O7-treatment, blood was drawn for estimation of renal injury markers in serum. Rats were then sacrificed, and their kidneys were dissected for biochemical and histopathological assays. K2Cr2O7-treated rats showed significant increases in markers of renal injury in serum, including blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), which were significantly (P < 0.05) decreased by PYC pre-treatment. Moreover, prophylactic pre-treatment of rats with PYC significantly (P < 0.05) ameliorated increased thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and protein carbonyl (PC), and decreased levels of glutathione (GSH) and catalase activity in the kidney homogenate of K2Cr2O7-treated rats. These results were also supported and confirmed with histopathological findings. The study suggests that PYC is effective in preventing K2Cr2O7-induced oxidative mediated nephrotoxicity, but more studies are needed to confirm the effects of PYC as a nephroprotective agent.

Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity.

Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. In the present work the effect of garlic powder, a recognized antioxidant, on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress was studied. Rats were fed a 2% garlic powder diet for 1 month. A single injection of K(2)Cr(2)O(7) (15 mg/kg) to rats induced tubule interstitial damage and an increase in the following markers of renal injury 2 days later: blood urea nitrogen (4.6-fold), serum creatinine (9.7-fold), proteinuria (35.9-fold), urinary excretion of N-acetyl-beta-d-glucosaminidase (12.9-fold) and glutathione-S-transferase (2.3-fold) and a decrease of 65% in serum glutathione peroxidase activity. In addition, K(2)Cr(2)O(7) injection increased the following nitrosative and oxidative stress markers in kidney: 3-nitrotyrosine (1.9-fold), 4-hydroxy-2-nonenal (2.1-fold), malondialdehyde (1.8-fold) and protein carbonyl content (1.7-fold). It was found that garlic powder feeding was able to prevent by 44-71% the alterations in the markers of renal injury studied, by 55% the histological damage, and by 47-100% the increase in markers of oxidative and nitrosative stress. It is concluded that the ability of garlic powder to ameliorate K(2)Cr(2)O(7)-induced renal injury is associated with its antioxidant properties. Our data support the use of garlic powder as a renoprotective agent.

Effects of dietary consumption of black tea infusion alone and in combination with known clastogens on mouse bone marrow chromosomes in vivo.

Black tea infusion in water, in concentrations simulating human consumption, was administered by gavage daily to male Swiss mice for 7 days. One set was given tea once daily and the other twice daily. The mice were then exposed to two known clastogens: chromium (VI) as potassium dichromate and mitomycin C on day 7, and killed after 24 hr. Chromosome damage was studied in preparations made from bone marrow following colchine injection of all mice, and examination of the cells after pretreatment in hypotonic solution, fixation, air drying one and staining with Giemsa solution. No effect was observed in mice given tea once daily. In mice administered tea twice daily, the frequencies of chromosomal aberrations and damaged cells were increased as compared with those of the control in distilled water. Administration of tea twice daily for 7 days could not reduce the clastogenic effects of mitomycin C significantly. The damage due to potassium dichromate was reduced significantly, almost to the level of distilled water. Dietary administration of black tea infusion could therefore significantly protect against clastogenic activity of chromium compounds though it was itself mildly clastogenic.