Nigerloxin

We have recently reported the beneficial influence of the fungal metabolite nigerloxin, a new aldose reductase inhibitor and a lipoxygenase inhibitor on oxidative stress in streptozotocin induced diabetic rats. In the present study we have investigated the antioxidant potential of nigerloxin in vitro as compared to one of the well known natural antioxidant, curcumin. The fungal metabolite nigerloxin was found to be an effective antioxidant in different in vitro assays including the phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH.),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS.+) and ferric reducing antioxidant power (FRAP) methods. The antioxidant potency of nigerloxin may be attributed to its electron donating nature. The ferric reducing potency of nigerloxin as demonstrated by FRAP assay method was even found to be superior to that of the natural antioxidant curcumin.

Background: The role of osmotic and oxidative stress has been strongly implicated in the pathogenesis of cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibition and improved antioxidant defense system in lens of diabetic rats. In the present study, the beneficial influence of nigerloxin was investigated in galactose-induced cataract in experimental animals. Methods: Cataract was induced in Wistar rats by feeding 30% galactose in diet. Groups of galactose-fed rats were orally administered with nigerloxin (25 and 100 mg/kg body weight/day) for 24 days. Results: Lens aldose reductase activity was increased significantly in galactose-fed animals. Lens lipid peroxides and advanced glycation end products were also significantly increased. Antioxidant molecule - reduced glutathione, total thiols and activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased in the lens of galactose-fed animals. Oral administration of nigerloxin once a day for 24 days at a dose of 100 mg/kg body weight, significantly decreased lens lipid peroxides and advanced glycation end products in galactose-fed rats. Lens aldose reductase activity was reduced and lens antioxidant molecules and antioxidant enzyme activities were elevated significantly by nigerloxin administration. Conclusions: The results suggest that alteration in polyol pathway and antioxidant defense system were countered by nigerloxin in the lens of galactose-fed animals, suggesting the potential of nigerloxin in ameliorating the development of galactose-induced cataract in experimental animals.

Elevated polyol pathway enzyme activities and oxidative stress play an important role in the development and progression of diabetic nephropathy. Here, we investigated the beneficial influence of nigerloxin, a fungal metabolite and a potent aldose reductase inhibitor and free radical scavenger in the kidney of streptozotocin-induced diabetic rats. A group of diabetic rats was orally administered with nigerloxin for 30 days (100 mg/kg). Diabetic rats showed increased lipid peroxides, advanced glycation end products (AGEs), elevated activities of polyol pathway enzymes, and lowered antioxidant defense system in kidney. Administration of nigerloxin decreased kidney lipid peroxides and AGEs. Activities of polyol pathway enzymes were reduced while activities of all antioxidant enzymes, glutathione, and ascorbic acid were elevated in the kidney of nigerloxin-treated diabetic rats. We also investigated antioxidant potential of nigerloxin in gentamicin-induced nephrotoxicity in Wistar rats. Groups of rats were orally administered with nigerloxin for 8 days (25 mg or 100 mg kg(-1) body weight day(-1)) along with gentamicin (80 mg/kg, i.p., for 8 days). Gentamicin induced increase in lipid peroxides, decrease in glutathione and activities of antioxidant enzymes in the kidney, and increase in blood creatinine, and urea concentrations were significantly countered by nigerloxin treatment. Thus, the results indicated the beneficial influence of nigerloxin on polyol pathway and oxidative stress associated with diabetes, which are implicated in ameliorating the development of diabetic nephropathy. Nigerloxin also ameliorated oxidative stress induced by gentamicin in the renal tissue.