The hepatoprotective and antioxidative effect of saffron stigma alcoholic extract against vincristine sulfate induced toxicity in rats

Abstract

Vincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment

“…(Singh et al, 2018), although not all results have always been positive, particularly in the case of vincristine. This increase in lipid peroxidation associated with liver toxicity (Harchegani et al, 2019) or peripheral neurotoxicity (Erdogan et al, 2020) caused by vincristine has been observed in treatments with cumulative doses of vincristine higher than those used in this study. Besides, it is important to mention that a slight but not significant increase in plasma levels of MDA was observed after two weeks of suspension of vincristine treatment.…”

Synchrotron Radiation FTIR Microspectroscopy Study of Biomolecular Alterations in Vincristine-Treated WRL68 Cells at the Single-Cell Level

“…30 The most wellestablished mechanism of how vincristine induces tumor cell death is that vincristine impairs the polymerization of mitotic spindle microtubules, causing cell division arrest in the metaphase and apoptosis in mitotic cells. 9,18 As reported previously, vincristine exerts antimitotic effects on both tumor and normal cells and causes both apoptosis and necrosis in normal hepatocytes. 9 Cell apoptosis may lead to structural changes in the cell lipid membrane, which are associated with lipid methylene vibrations.…”

“…9,18 As reported previously, vincristine exerts antimitotic effects on both tumor and normal cells and causes both apoptosis and necrosis in normal hepatocytes. 9 Cell apoptosis may lead to structural changes in the cell lipid membrane, which are associated with lipid methylene vibrations. 30,47 In the present study, increases in ν as (CH 2 )/ν as (CH 3 ) and ν s (CH 2 )/ν s (CH 3 ) indicated alterations in lipid structures and the presence of more longchain fatty acids in the vincristine-treated WRL68 cells.…”

Crocin Promotes Apoptosis in Human Ebv-Transformed B-Lymphocyte via Intrinsic Pathway

“…32,33 Some studies showed that the anti-proliferative activity of crocin like vincristine involves targeting microtubules 10 and p53-dependent and -independent mechanisms in colon cancer cells. 11,12 Crocin triggers apoptosis by increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma without affecting human normal fibroblast skin cells. 34 Also, Luo et al reported that the combination of crocin with cisplatin exerts growth suppression and apoptosis in gastric carcinoma cells.…”

“…9 Like vincristine, crocin's anti-proliferative activity involves targeting microtubules 10 or p53dependent and -independent mechanisms in cancer cells. 11,12 In our laboratory, we observed that crocetin, a hydrolyzed form of crocin, exerts anti-proliferative, proapoptotic, and pro-differentiating impacts on human leukemia cells by inhibiting protein kinase B (Akt)mediated pro-survival cascades, raising the intracellular Bcl-2-like protein 4 (Bax)/Bcl-2 ratio, and reducing Tyrosyl-DNA phosphodiesterase 1 (TDP1) enzyme activity and the expressions of promyelocytic leukemiaretinoic acid receptor alpha (PML-RARα), Histone deacetylase 1 (HDAC1), and Multidrug resistance (MDR)-associated proteins. 13,14 Our laboratory has been interested in crocin's application in lymphoma and leukemia.…”