Resveratrol and pterostilbene ameliorate the metabolic derangements associated with smokeless tobacco in estrogen deficient female rats

The impact of oral administration of resveratrol and pterostilbene daily for 60 days in estrogen deficient female rats that were simultaneously exposed to oral aqueous extract of smokeless tobacco (AEST) (100 mg/kg/day) was investigated. Estrogen deficiency was induced in rats by 30 days daily exposure to 4-vinylcyclohexene diepoxide (80 mg/kg, i.p.). The plasma nicotine and cotinine levels were quantified by HPLC. AEST exposure in estrogen deficient rats caused significant increase in body weight, changes in anthropometrical parameters, fasting serum glucose and insulin levels that indicated impaired glucose tolerance with insulin resistance. Serum AST, ALT, and ALP were elevated and activity of Na⁺K⁺ATPase in the skeletal muscle was decreased. Importantly, AEST exposure in rats impaired the hepatic and gastrocnemius muscle gene expressions of SIRT1, PGC-1α, PPAR-α, TFAM, NRF-1 and decreased the mitochondrial DNA content. Resveratrol and pterostilbene reversed these metabolic perturbations thus averting induction of metabolic syndrome in this milieu.