Therapeutic effects of P-glycoprotein activator rifampicin and antioxidant boswellia serrata when used alone and together in rats exposed to aflatoxin B1

Aflatoxin B1 (AFB1) is a toxic substance in many tissues, especially the liver, and is carcinogenic, mutagenic, teratogenic and immunosuppressive, especially with its effect on DNA. Rifampicin (Rif) is an antibiotic that inhibits nucleic acid synthesis and is also a stimulator of carrier proteins in tissues, and was used in the current study to reduce the absorption and increase the excretion from the body of AFB1, the substrate of these proteins. Boswellia serrata extract (BSE) has anti-inflammatory and antioxidant effects. This study aimed to determine the possible therapeutic effects of Rif and BSE on tissue damage in rats administered AFB1. A total of 63 Sprague-Dawley male rats were used in the study. Animals were divided into 9 groups: Control, corn oil, sodium carboxymethyl cellulose (CMC), Rif, BSE, AFB1, AFB1+Rif, AFB1+BSE, AFB1+Rif+BSE (n=7). The study period was determined as seven days and the animals were decapitated and blood, liver, kidney, intestine and brain tissues were collected. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine levels were determined in the blood. Malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) analyzes were performed in the tissues. Expressions of carrier proteins were measured by Western-blot technique. Additionally, blood and tissue AFB1 levels were analyzed by high-performance liquid chromatography (HPLC). Histopathological analyzes were performed on the tissues taken. AFB1 was detected in all tissues examined, most notably in the liver. While the expressions of p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in tissues decreased in the AFB1 group, they increased significantly in the Rif treated groups. AFB1 levels in tissues decreased due to the increase in these carrier proteins in the groups administered Rif and Rif+BSE together with AFB1. While AFB1 increased blood AST, ALT and creatinine levels, significant improvements were detected in the group administered Rif+BSE simultaneously with AFB1. It was observed that MDA levels in the liver and kidney tissues increased in the AFB1 toxicity group, whereas the increased MDA levels were effectively reduced in the Rif+BSE combined treatment group. In the tissue samples analyzed histopathologically, it was determined that AFB1 caused degeneration only in the liver tissue, and this degeneration was significantly reduced by Rif, BSE and Rif+BSE treatments. As a result, it was concluded that AFB1 showed signs of acute toxicity in the applied dosage regimen, whereas Rif + BSE combined treatments may offer more effective treatment options against the toxicity caused by AFB1.