Abstract
Background and AimCancer is a devastating disease with a severe impact on the physical and psychological well-being of patients. Hepatocellular carcinoma (HCC) has been reported in various species of animals including dogs, cats, sheep, and pigs. The present study aimed to study the immunohistochemical and histopathological changes andchemoprotective effect of aqueous and alcoholic extracts of Solanum nigrum on N-nitrosodiethylamine (NDEA)-induced HCC rat model.Materials and MethodsEighty-two male Wistar rats of 15 weeks of age weighing 200-250 g were selected for the experiment. They were randomly divided into ten groups. Group I served as normal control consisted of healthy rats. HCC was induced in Group II, IV, V, VI, VII, and X rats using NDEA as inducing agent followed by phenobarbitone as a promoter for 16 weeks. Group II rats were kept untreated as HCC control. Group III rats were kept as vehicle control (0.05% Sodium bicarbonate). Group IV and V rats were treated with aqueous extract of S. nigrum at 200 mg/kg and 400 mg/kg, respectively, and Group VI and VII rats were treated with an alcoholic extract of S. nigrum at 200 mg/kg and 400 mg/kg, respectively, daily orally for 28 days. Group X rats were treated withsorafenib as reference drug at a dose of 11.4 mg/kg daily orally for 28 days. Group VIII and IX rats were kept as aqueous and alcoholic extract control for studying the effect of the same on normal rats. Liver samples were collected to study the gross and histopathological lesions and the activity of cleaved caspase-3 and chemopreventive effect of aqueous and alcoholic extracts of S. nigrum on HCC.ResultsThe liver sections of rats from HCC control (Group II) showed loss of lobular architecture, necrosis, fatty change, enlarged and darkened nuclei with variable size, dilatation of hepatic sinusoids with Kupffer cell hyperplasia, dilatation and proliferation of bile duct, and intranuclear vacuoles and also showed the presence of more than one nucleolus. Administration of alcoholic extract of S. nigrum and sorafenib to NDEA/phenobarbital-treated rats reduced the severity of lesions in the liver. Immunohistochemical analysis of liver sections for caspase-3-positive cells of hepatic cancer-induced group showed immunoreactivity to rarely few. The immunoreactivity of the hepatocytes treated with a higher dose of alcoholic extract of S. nigrum was limited and was comparable to a standard drug, sorafenib.ConclusionOral administration of aqueous and alcoholic extracts of S. nigrum for 28 days showed significant rejuvenation in the structure of the liver in the histopathological section in a dose-dependent manner in rats.
Highlights
N-nitrosodiethylamine (NDEA) known as diethylnitrosamine (DEN), a hepatocarcinogen, is known to cause perturbations in the nuclear enzymes involved in deoxyribonucleic acid (DNA) repair/ replication and is normally used as a carcinogen to Copyright: Akshatha, et al Open Access
Liver of animals in Group IV, V, VI, and VII were found normal in appearance after the treatment with aqueous and alcoholic extract of S. nigrum
Liver of rats from Group III, VIII, and IX showed no gross lesions indicating that there is no effect of vehicle used in the experiment and aqueous and alcoholic extracts of S. nigrum
Summary
N-nitrosodiethylamine (NDEA) known as diethylnitrosamine (DEN), a hepatocarcinogen, is known to cause perturbations in the nuclear enzymes involved in deoxyribonucleic acid (DNA) repair/ replication and is normally used as a carcinogen to Copyright: Akshatha, et al Open Access. Induce liver cancer in animal models [1]. DEN has been shown to be metabolized to its active ethyl radical metabolite, and the reactive product interacts with DNA causing mutation, which would lead to carcinogenesis [2,3]. The present study aimed to study the immunohistochemical and histopathological changes and chemoprotective effect of aqueous and alcoholic extracts of Solanum nigrum on N-nitrosodiethylamine (NDEA)-induced HCC rat model
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