1,2-Dimethylhydrazine (DMH), an environmental toxicant specifically targets the colon. The present study was aimed to evaluate the efficacy of gallic acid (GA) against colon toxicity induced by DMH in Wistar rats. GA, a phenolic acid has numerous beneficial properties, which include antiviral, antifungal and antioxidant properties which help cells to overcome oxidative stress and balance the redox homeostasis. GA was administered orally at two doses (25 and 50 mg/kg body weight) once daily for 14 days and a single dose (40 mg/kg body weight) of DMH was administered subcutaneously on 14th day. Animals were sacrificed on the 15th day and we could find that GA at both the doses significantly ameliorates DMH-induced increased toxicity markers and also substantially increases the glutathione content level and activities of detoxifying enzymes. It also ameliorates the expression of proliferation, inflammation, apoptosis, goblet cell disintegration, and mucin depletion in the colon that was elevated upon administration of DMH. Histological alterations provide further confirmation of the protective role of GA against DMH-induced colon toxicity. The results of this study clearly indicate supplementation of GA is beneficial in ameliorating DMH-induced oxidative stress, inflammation, proliferation, apoptosis, mucin depletion, and goblet cell disintegration in colon of Wistar rats.

1,2 Dimethyl hydrazine (DMH), a cogent environmental toxicant, targets the colon. Previous reports suggest that DMH‐mediated dysregulation of the Wnt/β‐catenin pathway plays a vital role in the initial events of colon carcinogenesis. Our study was designed to investigate the effect of quercetin on DMH‐mediated colon cancer by targeting adenomatous polyposis coli (APC) and β‐catenin in Wistar rats. Animals were pretreated orally with quercetin at doses of either 25 or 50 mg/kg bodyweight (bw) and DMH at a dose of 20 mg/kg bw subcutaneously up to the 15th week and sacrificed after the 30th week. DMH administration leads to reactive oxygen species generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Increased inflammatory and proliferative proteins were observed in DMH‐induced colon cancerous rats. DMH treatment also led to dysregulation in the apoptotic pathway with decreased Bax:Bcl‐2 ratio. Quercetin pretreatment ameliorates DMH‐induced proliferation, activities of detoxifying enzymes, and putative early markers (mucin depletion and goblet cell disintegration) in colonic tissue. It also significantly regulates APC and β‐catenin expression and inhibits tumor incidence and multiplicity. Histological results further confirm the beneficial role of quercetin in averting DMH‐induced pathological alterations.

Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti-inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF-kB, COX-2, IL-6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin-100 and Diosmin-200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF-kB, COX-2, IL-6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]Pinduced oxidative stress and lung damage. K E Y W O R D S benzo(a)pyrene, diosmin, inflammation, lung injury, oxidative stress, pulmonary toxicity

Hesperidin (HD), a citrus bioflavonoid possesses a variety of biological activities including antioxidant, anti‐inflammatory, anti‐apoptotic and anti‐carcinogenic properties. In the present study, we investigated the effect of HD treatment on N,N′‐dimethylhydrazine (DMH) induced oxidative stress, inflammation, apoptosis and goblet cell disintegration in the colon of Wistar rats. Administration of HD was done at two doses (100 and 200 mg/kg body weight) orally to rats daily for 14 days followed by a single subcutaneous injection of DMH (40 mg/kg body weight) on the 14th day and next day animals were sacrificed. The protective potential of HD against colon toxicity was measured through membrane oxidation, antioxidant status, inflammatory and apoptotic markers expression, and histological changes. Results demonstrated that HD inhibited DMH mediated oxidative damage by diminishing the level of peroxidation of lipids and increasing the activity of superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione‐s‐transferase, and glutathione reductase. Moreover, HD attenuated inflammatory (NF‐кB, IL‐6, and COX‐2) and apoptotic (p38‐MAPK, p53, and caspase‐3) markers expression. HD also attenuated the DMH induced goblet cell disintegration and restored histoarchitecture of the colon. The results of the present study demonstrate that HD efficiently protects against DMH induced colon toxicity by modulating oxidative stress, inflammation, and apoptosis.

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