Chemoprevention Against Arsenic-Induced Mutagenic DNA Breakage and Apoptotic Liver Damage in Rat Via Antioxidant and SOD1 Upregulation by Green Tea (Camellia sinensis) which Recovers Broken DNA Resulted from Arsenic-H₂O₂Related in Vitro Oxidant Stress

Abstract

Green tea (Camellia sinensis; CS) strongly reverses/prevents arsenic-induced apoptotic hepatic degeneration/micronecrosis and mutagenic DNA damage in in vitro oxidant stress model and in rat as shown by comet assay and histoarchitecture (HE and PAS staining) results. Earlier, we demonstrated a link between carcinogenesis and impaired antioxidant system-associated mutagenic DNA damage in arsenic-exposed human. In this study, arsenic-induced (0.6 ppm/100 g body weight/day for 28 days) impairment of cytosolic superoxide-dismutase (SOD1), catalase, xanthine-oxidase, thiol, and urate activities/levels led to increase in tissue levels of damaging malondialdehyde, conjugated dienes, serum necrotic-marker lactate-dehydrogenase, and metabolic inflammatory-marker c-reactive protein suggesting dysregulation at the transcriptional/signal-transduction level. These are decisively restrained by CS-extract (≥10 mg/ml aqueous) with a restoration of DNA/tissue structure. The structural/functional impairment of dialyzed and centrifugally concentrated (6-8 kd cutoff) hepatic SOD1 via its important Cys modifications by H2O2/arsenite redox-stress and that protection by CS/2-mercaptoethanol are shown in in vitro/in situ studies paralleling the present Swiss-Model-generated rSOD1 structural data. Here, arsenite(3+) incubation (≥10(-8) μM + 10 mM H2O2, 2 hr) is shown for the first time with this low-concentration to initiate breakage in rat hepatic-DNA in vitro whereas, arsenite/H2O2/UV-radiation does not affect DNA separately. Arsenic initiates Fe and Cu ion-associated free-radical reaction cascade in vivo. Here, 10 μM of Cu(2+)/Fe(3+)/As(3+) +H2O2-induced in vitro DNA fragmentation is prevented by CS (≥1 mg/ml), greater than the prevention of ascorbate or tocopherol or DMSO or their combination. Moreover, CS incubation for various time with differentially and already degraded DNA resulted from pre-incubation in 10 μM As(3+)-H2O2 system markedly recovers broken DNA. Present results decisively suggest for the first time that CS and its mixed polyphenols have potent SOD1 protecting, diverse radical-scavenging and antimutagenic activities furthering to DNA protection/therapy in arsenic-induced tissue necrosis/apoptosis.

Epigallocatechin-Gallate and Theaflavin-Gallate Interaction in SARS CoV-2 Spike-Protein Central-Channel with Reference to the Hydroxychloroquine Interaction: Bioinformatics and Molecular Docking Study

“…Earlier our laboratory has demonstrated the anti-carcinogenic role of green tea extract [13,14]. It decisively helps in DNA protections by scavenging free radicals and that efficacy was found to be even greater than the known specific radical-scavengers [14,15]. According to the relationships between structure and antiviral activity of catechin derivatives, the 3-galloyl and 5′-OH group of catechin derivatives appear critical to antiviral activities [22].…”

“…Tea flavonoids have been demonstrated as strong anti-toxicant, anti-oxidant and anti-inflammatory agents. Anti-tumerigenic role of catechin derivatives especially EGCG has been shown decisively by several laboratories [13,14,15]. Regarding the anti-viral role tea flavonoids have been shown to be strong agent [16].…”

Natural Antioxidants Against Arsenic-Induced Genotoxicity

“…The antioxidant treatments have been reported to enhance the antioxidative capacity of these enzymes [57,122]. Recently, Acharyya et al [141] have shown upregulation of SOD and CAT activities by green tea extract in rats as well as in vitro using rat liver cells. They also showed that green tea extract was effective in the prevention of arsenic-induced hepatic tissue and DNA damage via restoration of arsenic-depleted hepatic xanthine oxidase (XO) and serum uric acid levels.…”

Therapeutic properties of green tea against environmental insults

“…The beneficial effects of green tea on arsenic-associated toxicities were summarized in Table 5 [117–130]. Green tea and its principal polyphenol, (−)-EGCG, efficiently counteracted the cytotoxic effects of arsenic compounds in Chinese hamster lung fibroblast V69 cells [128].…”

“…GTE reduced arsenic-induced formation of 8OHdG and induced arsenic-suppressed DNA repair enzymes, such as PARP1, DNA β-polymerase, XRCC1, DNA ligase III, DNA protein kinase (catalytic subunit), XRCC 4, DNA ligase IV, and DNA topoisomerase Iiβ, in Swiss albino mice [127]. GTE (≥10 mg/ml aqueous) restored arsenic-induced mutagenic DNA breaks and liver damages in rats via upregulation of cytosolic SOD [117]. Similarly, supplementation of tea extracts (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w.…”