The protective effect of an ethanol extract of Curcuma comosa against cisplatin-induced renal toxicity in mice was studied. Adult male mice were pretreated for 4 days with the ethanol extract of C. comosa [100-200 mg/kg body weight (BW), orally (p.o.)] before injection of cisplatin (12.5 mg/kg BW, intraperitoneally (i.p.)). Five days later the mice were killed, and blood samples were collected to determine blood urea nitrogen (BUN) and plasma creatinine levels. Kidneys were examined histopathologically and levels of lipid peroxidation, gluthathione (GSH) content, and superoxide dismutase (SOD), gluthathione peroxidase (GPx), and catalase (CAT) activities were determined. Histological examinations revealed degenerative changes and tubular necrosis in mice treated with cisplatin, which were improved by pretreatment with C. comosa ethanol extract. Cisplatin raised BUN, creatinine, and kidney lipid peroxidation levels, and lowered kidney GSH content and levels of GPx, SOD, and CAT activities, all of which (except SOD and CAT) could be restored to normal values by pretreatment with 200 mg/kg BW of C. comosa ethanol extract. In addition, the ethanol extract of C. comosa and its isolated diarylheptanoid compound also exhibited radical scavenging activities. The results suggest that the ethanol extract of C. comosa exhibits effective protection against cisplatin-induced nephrotoxicity mediated through its antioxidant activity.

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Methamphetamine (METH) is a highly addictive CNS stimulant that its long-term use is associated with the loss of neurons in substantia nigra and development of Parkinson's disease later in life. Common form of METH is Ya-Ba tablet, in which, large portion of caffeine is added to the mass to enhance the stimulatory effect. Previous study demonstrated that caffeine potentiates the toxic effect of METH in association with the production of reactive oxygen species and the induction of apoptosis. Since METH causes induction of autophagy, the question was raised whether this pathway participates in the potentiating effect of caffeine on METH neurotoxicity. We used SH-SY5Y, a neuroblastoma cell line, as an in vitro model to study the effect of METH and caffeine. Co-treatment of non-toxic concentrations of METH, at 0.5 mM, and caffeine, at 1 mM, caused reduction of the cell viability. Reduction of the cell viability was associated with attenuation of autophagy, demonstrated by reduction of LC3-II levels and the number of autophagosome puncta, together with increase of caspase-3 activation. Similar effect was produced by treatment with autophagy inhibitors, 3-MA and wortmanin. Our results suggested that caffeine potentiates METH toxicity through inhibition of autophagy and that autophagy serves as a protective mechanism. In conclusion, we proposed the augmented hazard associated with caffeine and METH combination in Ya-Ba abusers.

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