Evaluation of mutagenic, cytotoxic, mitochondrial dysfunction, apoptotic activity, and acute toxicity of ethanolic extract of Cissus quadrangularis. (1st January 2023)

• Record Type: Journal Article
• Authors: Syed, Anees Ahmed; Reza, Mohammad Irshad; Kalleti, Navodayam; Husain, Athar; Singh, Pragati; Rath, Srikanta Kumar; Gayen, Jiaur R.
• Is Part Of: Toxicology. Volume 483(2023)
• Publication Date: 2023-01-01
• Subjects: AIF Apoptosis-inducing factor -- ATP Adenosine Triphosphate -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM Dulbecco's Modified Eagle Medium -- FBS Fetal Bovine Serum -- H & E Hematoxylin and Eosin -- JC-1 Tetraethylbenzimidazolylcarbocyanine iodide -- LDH Lactate dehydrogenase -- MMP Mitochondrial membrane potential -- MTT 3-(4, 5-dimethylthiazol-2-yl)− 2, 5-diphenyltetrazolium bromide -- NAD Nicotinamide Adenine Dinucleotide -- ROS Reactive oxygen species -- SRB Sulforhodamine-B; Cissus quadrangularis -- Mutagenicity -- Cytotoxicity -- Mitochondrial dysfunction -- Apoptosis -- Metabolic disorders; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2022.153373
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Recent studies have focused on exploring the efficacy of Cissus quadrangularis extract (EECQ) against various metabolic disorders involving the liver as the prime target organ, suggesting a considerable threat of hepatotoxicity in the person encountering it. Consequently, the current study was aimed to unravel the mutagenic, cytotoxic, mitochondrial dysfunction, apoptotic activity in HepG2 cells, and acute toxicity of EECQ. MTT, SRB, trypan blue dye exclusion, and lactate dehydrogenase (LDH) assay were performed in HepG2 cell lines to determine the cytotoxicity of the extract. The mutagenic potential was determined by the Ames test using various strains of Salmonella typhimurium. Acute toxicity was done at a dose of 2000 mg/kg in Sprague Dawley rats. MTT and SRB cytotoxicity assays demonstrated dose-dependent cytotoxicity of extract. The three highest noncytotoxic doses from the above assay, investigated by trypan blue dye exclusion and LDH assay, did not reveal cytotoxicity. Besides, mitochondrial dysfunction was determined by measuring cellular and mitochondrial ROS, ATP, NAD, mitochondrial membrane potential, Bax/Bcl2 ratio, mitochondrial and cytoplasmic cytochrome c, and apoptosis-inducing factor, were found to be equivalent in both extract exposed and unexposed cells. Moreover, the apoptotic cell morphology and the expression of pro-apoptotic mRNAs and proteins were equivalent in both the group. In acute toxicity, EECQ in rats did not cause any significant change in body weight, liver index, and liver function test. All-encompassing, the present study unraveled that EECQ is not mutagenic, cytotoxic, nor apoptotic in human hepatic cells, as well as neither acute toxicity. Graphical Abstract: ga1 Highlights: Cissus quadrangularis demonstrated dose-dependent cytotoxicity in HepG2 cells. Cissus quadrangularis is not mutagenic and apoptotic in human hepatic cells. Cissus quadrangularis is depicted to be safe in acute toxicity study. Cissus quadrangularis did not cause mitochondrial dysfunction in HepG2 cells