Possible involvement of Protein Tyrosine Phosphatase in Alcoholic Cardiomyopathy

Abstract

Protein tyrosine phosphatases (PTPase’s) are the enzymes that dephosphorylate survival kinase PI3K/Akt pathway this may be a key mechanism in alcohol-induced cardiomyopathy. Therefore, the present study was designed to investigate the role of PTPase in alcohol-induced cardiomyopathy. Ethanol (20%) at the dose of 7.9 g/kg P.o was given regularly for 60 days that produced Alcohol-induced Cardiomyopathy (ACM). CM (cardiomyopathy) was assessed in terms of decrease in LVDP, dp/dtmax, dp/dtmin, LV protein content, CFR and increase in LVEDP, LVW/BW, MABP, LV collagen, LV cholesterol content, TNF-α, nitrite levels and iNOS expression in alcoholic cardiomyopathic rats. Sodium Orthovanadate (SOV) (PTPase inhibitor) at the dose of 2.5, 5 and 10mg/kg significantly increased LVDP, dp/dtmax, dp/dtmin, CFR, LV protein content. Moreover, significant decrease in the elevated MABP, LVEDP, LVW/BW, LV collagen, LV cholesterol content, nitrite, TNF-α and iNOS level was observed. Furthermore, administration of SMT (S-methylisothiourea), an iNOS inhibitor (5mg/kg., i.p) with SOV (10mg/kg., p.o) significantly increased the ameliorative effect of SOV (10mg/kg., p.o). The findings suggested that PTPases may have a function in regulating alcohol-induced cardiomyopathy by interfering with Akt/Pi3k and its downstream pathways, which include TNF-alpha and iNOS.