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Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidence suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Aulosira fertilisima Ghose (EEA) was evaluated using cisplatin (5 mg/kg−1 i.p.)-induced renal damage in rats. EEA showed higher significant effect on DPPH radical scavenging activity as compared with methanol extract of A. fertilisima (MEA) and water extract of A. fertilisima (WEA). Thus, EEA was selected for further in vivo studies. The serum urea and creatinine levels in the cisplatin alone-treated group were significantly elevated with respect to normal group of animals. The levels were reduced in the EEA (100 mg/kg, p.o) plus cisplatin-treated groups. Renal oxidative stress was determined by renal TBARS, CD and reduced glutathione levels, and by enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin-produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the study indicated that A. fertilisima significantly and dose-dependently protected the nephrotoxicity induced by cisplatin. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidence has implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Aphanizomenon flos-aquae (AFA), blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of AFA against cisplatin-induced oxidative stress and renal dysfunction. The ethanolic extract of Aphanizomenon flos-aquae (EEAFA) (25, 50, 100 mg/kg-1 p.o.) was administered two days before through three days after cisplatin challenge (5 mg/kg-1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEAFA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of AFA in cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Search for novel anticancer lead molecules continues to be a major focus of cancer research due to the limitations of existing drugs such as lack of tumor selectivity, narrow therapeutic index and multidrug resistance of cancer types. Natural molecules often possess better pharmacokinetic traits compared to synthetic molecules as they continually evolve by natural selection process to interact with biological macromolecules. Microbial metabolites constitute nearly half of the pharmaceuticals in market today. Endophytic fungi, owing to its rich chemical diversity, are viewed as attractive sources of novel bioactive compounds. In the present study, we report the purification and characterization of a novel steroidal saponin, cholestanol glucoside (CG) from Saraca asoca endophytic fungus Lasiodiplodia theobromae. The compound was assessed for its cytotoxic potentialities in six human cancer cell lines, A549, PC3, HepG2, U251, MCF7 and OVCAR3. CG exhibited significant cytotoxicities towards A549, PC3 and HepG2 among which A549 cells were most vulnerable to CG treatment. However, CG treatment exhibited negligible cytotoxicity in non malignant human lung fibroblast cell line (WI-38). Induction of cell death by CG treatment in A549 cells was further investigated. CG induced the generation of reactive oxygen species (ROS) and mitochondrial membrane permeability loss followed by apoptotic cell death. Mitochondrial membrane depolarization and apoptotic cell death in CG treated A549 cells were completely blocked in presence of an antioxidant, N-acetyl cysteine (NAC). Hence it could be concluded that CG initiates apoptosis in cancer cells by augmenting the basal oxidative stress and that the generation of intracellular ROS is crucial for the induction of apoptosis.

Paracetamol caused liver damage as evident by significant increase in the activities of aspartate and alanine transferases. There were general statistically significant losses in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione transferase and an increase in thiobarbituric acid reactive substances in the liver of paracetamol treated group compared with the control group. However, treatment with ethanol extract of A. flos-aquae (EEAFA) was able to counteract these effects. Protection offered by silymarin (standard reference drug) seemed relatively greater. The results suggest that EEAFA can act as hepatoprotective agent against paracetamol induced toxicity as an antioxidant.

Free radicals cause cell injury, when they are generated in excess or when the antioxidant defense is impaired. Carbon tetrachloride (CCl4) is used as a model for liver injury. In this study antioxidant activity of ethanol extract of A. fertilisima (EEA) was investigated using CCl4 intoxicated rat liver as the experimental model. Oral administration of EEA at a dose of 100 mg/kg body weight, for 14 consecutive days, the rate of the production of antioxidant enzymes like super oxide dismutase, catalase, glutathione peroxidase and glutathione transferase in rats compared to the CCl4 treated group without any supporting treatment. Liver damage is detected by the measurement of the activities of serum enzymes like aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and alkaline phosphatase which were released in to the blood from damaged cells. The normalization of these enzymes levels was observed in rats treated with EEA (100 mg/kg body weight) by reducing the leakage of the above enzymes in to the blood. The findings provide a rationale for further studies on isolation of active principles and its pharmacological evaluation. Protection offered by silymarin (standard reference drug) seemed relatively greater.