The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity

Abstract

The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA( 20 mg/kg, SC) and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), albumin, and histopathological changes of liver were examined.Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4 and expression of Bax and Bcl2 using were also done.CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT and γGT; a decrease in serum albumin and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituricacid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, increased hepatic activity of NF-κB, and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis and inflammation.

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats

“…In addition, Alessandro and coworkers reported that testosterone decreased ROS production by binding to cytoplasmic androgen receptor (AR) and promoting its translocation to the nucleus, resulting in enhanced extracellular matrix (ECM) production via the transcription-inducing complex c-FOS/c-JUN (Bertolo et al 2014). Moreover, previous studies demonstrated that both testosterone (Mancini et al 2008, Zhang et al 2013 and vildagliptin (Avila Dde et al 2013, El-Sherbeeny & Nader 2016 could decrease oxidative stress by increasing the antioxidative substance such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). This hypothesis is supported by the findings in this study that HFO and NDO groups had increased cardiac mitochondrial ROS production and that both testosterone and vildagliptin effectively attenuated cardiac mitochondrial ROS levels and reduced mitochondrial dysfunction (Chinda et al 2014.…”

Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury

“…The limitations of our study included: the use of a single dose of vildagliptin and this was based on the fact that this dose showed protective effect in previous studies [10,28,48]; and a group with vildagliptin alone had not been done as the safety of vildagliptin was reported in healthy subjects in both experimental and clinical studies [48,49].…”

Dipeptidyl Peptidase-4 Inhibitors and Inflammation: Dpp-4 Inhibitors Improve Mean Pleatelet Volume and Gamma Glutamyl Transferase Level

“…Increased levels of GGT have been shown to be associated with subclinic inflammation [42], CVS and metabolic diseases [43] [44]. It has been shown that cyclosporine hepatotoxicity is less in vildagliptin-given rats and has a positive effect on serum GGT [45]. In a Japanese study of type 1 diabetes, the correlation between DPP-4 activity and serum GGT was noted.…”