Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino Wistar rats

Abstract

BackgroundHepatocellular Carcinoma (HCC) is among the most lethal cancers (five-year survival rates under 11%), which makes it the third most frequent cause of cancer related deaths in men and sixth in women. Still there are limited treatments available for majority of HCC at advanced stages. Systemic chemotherapy for advanced hepatocellular carcinomas, either as single-agent therapy or in combination, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib are some to bank upon.Aim: This study is an attempt to evaluate the synergistic chemopreventive potential of Loperamide (5mg/kg) in combination with Niacin in hepatocarcinogenic rats. When challenged by a single diethylnitrosamine (DENA) (160 mg/kg). Material and methods:The ability to treat hepatocellular carcinoma was measured by comparing biochemical serum markers such as glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), acid phophatase (AP), cholesterol (C), triglycerides (TG) and high density lipoproteins (HDL), total proteins (TPR), bilirubin and the specific marker for hepatocellular carcinoma such as alpha fetoprotein (AFP). The caspase-3 activity was also evaluated to decipher the potential of the drug as well as to explore the possible mechanism. Results:The results have revealed the significant elevation of these parameters in DENA control group compared to normal control and the therapeutic groups. Casepase-3 activity was found to be highly elevated in the therapeutic group. Histopathology result also revealed severe the changes in hepatic tissues. Disease control animals showed central veins surrounded by extensive necrosis and inflammatory infiltrate, clusters of hepatocyte necrosis and the portal tract with bile duct proliferation and marked atypia. Liver section from loperamide with niacin control group shows the normal architecture of the liver, no necrosis was observed. ConclusionOur data indicates that this remarkable combination possess the potential for the treatment of hepatocellular carcinomas in rats exposed to DENA. Administration of Loperamide + Niacin relatively improved the biochemical parameters to values approximating those of the normal controls via increasing the Caspase-3 activity in them and inducing Apoptosis in cancerous cells.

Combination of Loperamide and Niacin modify DENA induced altered Liver enzymes

“…Its effect on intestinal motility is well established. [15] The apoptosisinducing activity of Loperamide has also been reported by the researchers [16,17] may be by promoting caspase 3 activity. In this hypothesis we are trying to evaluate the liver function profile altered or restored by the synergistic activity by Loperamide and Niacin.…”

“…These enzyme generally elevate and squeeze out of the liver cells during necrosis or hepatitis whether chronic hepatitis or cholestitis hepatitis. It has also been observed and established by the researchers that SGPT, SGOT, serum bilirubin level elevates significantly after DENA exposure in the experimental animals [19,17] . In present study serum SGPT and SGOT levels elevated significantly (p<0.001) in all groups exposed to DENA as compared to the NC group.…”

Deconvoluting the dual hypoglycemic effect of wedelolactone isolated fromWedelia calendulacea: investigationviaexperimental validation and molecular docking

“…The hepatic parameters, namely alkaline phosphatase (AST), aspartate aminotransferase (AST), alanine transaminase (ALT); serum renal parameters, including blood urea nitrogen (BUN), total protein, creatinine, albumin; lipid parameters, such as total cholesterol (TC), high density lipoprotein (HDL), triglyceride (TG), very low density lipoprotein (VLDL) and, low density lipoprotein (LDL), were scrutinized using commercially available diagnostic kits. The atherogenic index and coronary risk index were scrutinized as per the given formula: [24][25][26][27][28][29][30][31] Inammatory and pro-inammatory mediators Pro-inammatory cytokines, namely interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), and inammatory mediators, such as C-reactive protein (CRP), were also estimated as per the instructions in the available commercial kits.…”

Dendrimer-conjugated podophyllotoxin suppresses DENA-induced HCC progression by modulation of inflammatory and fibrogenic factors

“…27 Lesions in liver tissues have been reported earlier to be due to elevated levels of liver enzymes causing damage to the tissue. 28,29 The histopathological studies showed that DENA treatment caused complete distortion of liver histology and led to proliferation of bile ducts, anisocytosis, anisokaryosis and karyomegaly. The infiltration of inflammatory cells was also observed along with the degenerative changes.…”