Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin

Pir Mohammad Ishfaq; Shivani Mishra; Anjali Mishra; Zaved Ahmad; Shovanlal Gayen; Subodh Kumar Jain; Swati Tripathi; Siddhartha Kumar Mishra

doi:10.1016/j.crphar.2022.100118

Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin

Curr Res Pharmacol Drug Discov. 2022 Jul 8:3:100118. doi: 10.1016/j.crphar.2022.100118. eCollection 2022.

Authors

Pir Mohammad Ishfaq^{1

2}, Shivani Mishra¹, Anjali Mishra¹, Zaved Ahmad¹, Shovanlal Gayen³, Subodh Kumar Jain², Swati Tripathi⁴, Siddhartha Kumar Mishra^{1

5}

Affiliations

¹ Cancer Biology Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, 470003, (M.P.), India.
² Molecular Biology Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, 470003, (M.P.), India.
³ Department of Pharmaceutical Sciences, Dr. Harisingh Gour Central University, Sagar, 470003, (M.P.), India.
⁴ Amity Institute of Microbial Technology, Amity University, Noida, 201313, (U.P.), India.
⁵ Department of Biochemistry, University of Lucknow, Lucknow, 226007, (U.P.), India.

Abstract

Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (Inonotus obliquus) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of Inonotus obliquus (IOAE). Adult Balb/c mice were administered with MC-LR at 20 μg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 ± 3.3 μM) which were regained by IOAE treatment (50.83 ± 3.0 μM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 μg MC-LR/mL as that of control 100% Cell viability. The IC₅₀ was calculated to be 3.6 μg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.

Keywords: Antiinflammation; Apoptosis; Chaga mushroom; Hepatotoxicity; Microcystin-LR.