Oncogenic challenge of bromocriptine and L-arginine versus conventional antidiabetics on diethyl nitrosamine-induced liver tumorigenesis in diabetic rats: focus on AMPK activation

Background: Diabetes mellitus (DM) is associated with a spectrum of cancers where the metabolic antecedents, consequences, and therapy might affect cancer risk. The association between hepatocellular carcinoma (HCC) DM had been confirmed. Approaches to HCC prevention focus on molecular regulators disease process defined as inflammation-fibrosis-cancer axis. AMP-activated protein kinase (AMPK) an interesting tumor suppressor promising target for therapy. This study aimed investigate effects bromocriptine mesylate L-arginine hepatic carcinogenesis rat model neoplasia induced by diethyl nitrosamine (DENA) promoted type-2 in contrast conventional antidiabetics.Methods: One hundred male Wistar rats were randomly assigned into two sets; control set (normal, HCC, DM, combined HCC/DM) treated received one following drugs another 5 weeks: insulin glargine, glimepiride, metformin, pioglitazone, mesylate, or L-arginine. Bodyweight changes, blood glucose level, liver functions tests, serum C-peptide alpha-fetoprotein (AFP), activated AMPK assessed beside histopathological changes.Results: Equivalent treatment significantly reduced AFP, despite their minor glycemic control. activation, yet less than metformin. Histopathologic examination revealed reduction intra-lobular chronic inflammatory cell infiltration, steatosis necrosis bromocriptine, Hepatic necro-inflammatory changes most prominent insulin-treated rats.Conclusions: prevent early neoplastic almost equivalent metformin at least partially via activation.