Victor Nedzvetsky, Grigoriy Andrievsky, Tamar Chachibaia and Artem Tykhomyrov
Background: Diabetes mellitus causes damage to many vital organs, including brain and liver, mostly due to excessive free radical generation and development of oxidative stress. Some water-soluble forms of C60 fullerene and their hydrated nanostructures are proposed for prevention as well as treatment of various pathological conditions caused by oxidative stress.
Aim of the study: Assessment and comparison of antioxidant effects of hydrated C60 fullerene (C60HyFn) in brain and liver of rats with experimental streptozotocin (STZ)-induced hyperglycemia and evaluation of possible neuroprotective capacity of C60HyFn acting as potent agent to suppress reactive astrocytosis. Materials and methods: To induce hyperglycemia, male Wistar rats received single intraperitoneal (i.p.) injection of STZ in a dose of 45 mg/kg body weight (b.w). Thirty five rats were divided into 5 groups (7 animals per group): Group I (control, saline-injected rats); Group II (STZ-diabetic rats); Group III (rats injected with C60HyFn in a dose of 0.3 mg/kg b.w–C60HyFn control); Group IV (rats received single i.p. injection of C60HyFn in the same dose one week prior to STZ injection – prophylactic regime); Group V (rats received single i.p. injection of C60HyFn in the same dose one week after development of stable hyperglycemia–therapeutic regime). The following parameters were assessed in the groups of control and experimental animals: blood glucose concentration, levels of end-products of lipid peroxidation (LPO) and carbonylated proteins as markers of protein oxidative modifications (POM) in liver and brain tissues. Levels of astrogliosis in various sections of rat brain were monitored as additional parameter of C60HyFn neuroprotection. Immunochemical and immunohystochemical determination of glial fibrillary acidic protein (GFAP) as sensitive marker of astrocyte response were applied to evaluate intensity of astrocyte reactivity.
Results: STZ induced consistent hyperglycemia accompanied by extended oxidative damage of lipids and proteins in rats’ central nervous system (CNS) and liver. Beneficial effects of C60HyFn on oxidative status in liver of rats with hyperglycemia were observed in both regimes of administration. However, C60HyFn markedly reduced abnormally high levels of macromolecule oxidation in diabetic brain tissues only when used in therapeutic regime. In addition, diabetic rats were characterized by significant elevation of GFAP levels due to increase of astrocyte reactivity in brain cortex and hippocampus. C60HyFn treatment restored GFAP levels near to normal supposedly by lowering of astrogliosis caused by hyperglycemia. Though, C60HyFn, serving as high-performance antioxidant and alleviating harmful side-effects of diabetes such as oxidative stress, does not affect the blood glucose levels in diabetic rats and therefore not remove the prime cause of metabolic disturbance.
Conclusion: Nanostructures of hydrated C60 fullerene have been shown to exert beneficial effects in brain and liver of rats with STZ-induced diabetes mainly through the diminution of oxidative stress and can be applied for prevention and treatment of diabetic complications such as liver injury and neuropathy.