Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats

This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatin-induced liver toxicity. A total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, propionyl-l-carnitine (500 mg/kg), and d-carnitine (500 mg/kg), respectively, for 10 successive days. The fourth, fifth and sixth groups were injected intraperitoneally with the same doses of normal saline, propionyl-l-carnitine and d-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Administration of the standard nephrotoxic dose of cisplatin did not produce any changes in serum alanine transaminase and gamma-glutamyl transferase and no morphological changes in liver tissues. However, it did produce a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione content in liver tissues. On the other hand, combined treatment with cisplatin and d-carnitine induced a dramatic increase in serum alanine transaminase and gamma-glutamyl transferase, as well as progressive reduction in total carnitine and ATP content in liver tissue. Moreover, histopathological examination of liver tissues confirmed the biochemical data, where cisplatin and d-carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl-l-carnitine, cisplatin did not produce any biochemical and histopathological changes in liver tissues. In conclusion, data from this study suggest for the first time that (1) carnitine deficiency is a risk factor and could precipitate cisplatin-induced hepatotoxicity, (2) oxidative stress is not the main cause of cisplatin-related hepatotoxicity and (3) propionyl-l-carnitine prevents the development of cisplatin-induced liver injury.     

Protective effect of -arginine against nephrotoxicity induced by cyclosporine in normal rats

Effects of L-arginine (L-arg) and aminoguanidine (AG) on the nephrotoxicity induced by cyclosporine (CsA) were investigated. After injection of CsA (15 mg kg(-1) day (-1)i.p. for 10 days), it induced nephrotoxicity, manifested biochemically by a significant elevation of serum urea and creatinine. In addition, a marked increase in lipid peroxides measured as malondialdehyde (MDA) as well as a significant decrease in glutathione peroxidase (GSH-Px) activity (EC.1.11.1.9) and reduced glutathione content (GSH) in kidney tissues homogenate were observed. Nephrotoxicity was further confirmed by histopathological investigation. Oral administration of L-arg (300 mg kg (-1)day(-1) orally) for 5 days before and 10 days concomitant with CsA injection produced a significant protection against nephrotoxity induced by CsA. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, L-arg prevented the rise of MDA as well as reduction of GSH-Px activity and reduced GSH content in kidney tissue. The protective effects of L-arg against CsA-induced nephrotoxicity were further confirmed by histopathological examination. However, oral supplementation of AG (100 mg kg (-1)day(-1) p.o.) did not protect the kidney from the damaging effects of CsA. These results suggest that L-arg can ameliorate kidney dysfunction induced by CsA via a mechanism(s) which involves the production of nitric oxide. In addition, L-arg may therefore be a beneficial remedy for CsA nephrotoxicity and can be used to improve the therapeutic index of CsA.     

Studies on the cytological and biochemical effects of valerian in somatic and germ cells of Swiss albino mice.

Valerian is widely known for its use as a sedative and an anti-anxiety drug in the folk medicine. Literature reports suggested valerian to induce genotoxicity in vitro (ECV304 cells) by reactive oxygen species-mediated mechanism; however, there are no reports on its genotoxicity and/or the epigenetic mechanism in vivo. In view of the folkloric significance, it was found worthwhile to (1) determine the genotoxic effects of valerian in somatic and germ cells of mice and (2) investigate the role of epigenetic mechanisms. The protocol included the oral treatment of mice with different doses (500, 1000 and 2000 mg/kg/day) of valerian for 7 days. The following experiments were conducted: (i) cytological studies on micronucleus test, (ii) cytogenetic analysis for meiotic chromosomes, (iii) cytological analysis of spermatozoa abnormalities, (iv) quantification of proteins and nucleic acids in testicular cells and (v) estimation of malondialdehyde (MDA) and nonprotein sulfhydryl (NP-SH) in hepatic and testicular cells. The treatment increased the frequency of micronuclei in the polychromatic erythrocytes (PCE) and decrease the ratio of PCE to normochromatic erythrocytes (NCE) in the femur. It caused aberrations in chromosomes of the testis and induced spermatozoa abnormalities. The concentration of nucleic acids was depleted in the testicular cells. These changes might be attributed to the epigenetic mechanisms as revealed by an increase in the concentrations of MDA and a decrease of NP-SH levels in hepatic and testicular cells observed in the present study. The observed changes may be ascribed to terpenoids (valepotriates) and flavonoids (6-methylapigenin and 2S(-)-hesperidin) present in valerian.     

Traditional medicinal knowledge of plants used for cancer treatment by communities of mountainous areas of Fez-Meknes-Morocco

BackgroundSince their existence on earth, humans have used herbal medicine to meet their requirements for medication. The aim of the study: This work refers to a study conducted to carry out an ethnopharmacological survey of medicinal plants used for the treatment of cancer in Fez-Meknes region of Morocco. Material and Methods: To achieve this goal, 300 informants including 237 local people and 63 herbalists. They were requested to fill a survey related questionnaire aiming at the collection of data about the addressed objective. Informants were asked about the vernacular names, parts of medicinal plants used, mode of preparation, route of administration, reference area as well as the ecological distribution. The Relative Frequency of Citation (RFC) and Fidelity Level (FL) were calculated to identify the most effective plants recommended by informants for disease treatment. Results: The findings obtained in the present survey revealed that 94 species belonging to 47 families have been used for cancer treatment in the region of Fez-Meknes. Fruits, leaves, and seeds are the most commonly used plant parts, by the time powder and infusion arethe most common methods used fordrug preparations. Conclusion: This work may contribute towards the society as it provides interesting data on traditional medicinal knowledge of medicinal plantsused to fight cancer.