Toxicology International (Formerly Indian Journal of Toxicology)

Ferial Majed ¹, Sana Nafees ¹, Summya Rashid ¹, Nemat Ali ¹, Syed Kazim Hasan ¹, Rashid Ali ¹, Ayaz Shahid ¹, Sarwat Sultana ¹

Affiliations
1 Department of Medical Elementology and Toxicology, Section of Molecular Carcinogenesis and Chemoprevention, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, IN

Abstract

Objective: The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the précised underlying mechanism remains to be elucidated. Materials and Methods: In light of the important role of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues. Results: We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage. Conclusion: The findings of the present study suggest that the chemopreventive effect of TC is associated with upregulation of endogenous cytoprotective machinery and downregulation of inflammatory mediators (inhterleukin (IL)-6, COX-2, i-NOS, ODC, and NF-κB).

Keywords

Cytokines, Inflammation, Proinflammatory Markers, Terminalia chebula, Skin Carcinogenesis.

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Sana Nafees , Nemat Ali , Summya Rashid , Syed Kazim Hasan , Sarwat Sultana

Abstract

Objectives: In the present study we have evaluated the chemopreventive efficacy of Bauhinia purpurea against Diethylnitrosamine (DEN) initiated and 2 Acetylaminofluorine (2‑AAF) promoted hepatocarcinogenesis in Wistar rats. Materials and Methods: Efficacy of Bauhinia purpurea against 2‑AAF‑induced hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities (reduced hepatic GSH, glutathione peroxidase, glutathione reductase, catalase, and quinone reductase), histopathological changes and expressions of early tumor markers viz., ornithine decarboxylase activity (ODC) and proliferating cell nuclear antigen (PCNA) and also expressions of p53, Bax, Bcl‑2, and caspase‑3 were evaluated. Results: Oral pretreatment with B. purpurea significantly decreased the levels of serum toxicity markers, elevated antioxidant defense enzyme activities, suppressed the expression of ODC and PCNA and P53 along with the induction of apoptosis in the pretreatment groups. Tumor incidences are reduced by pretreatment of B. purpurea. Histopathological findings revealed that B. purpurea‑pretreated groups showed marked recovery. Conclusion: The results support the protective effect of B. purpurea against chemically induced liver cancer and acts possibily by virtue of its antioxidant, antiproliferative, and apoptotic activities.

Keywords

Apoptosis, Bauhinia purpurea, chemoprevention, hepatocarcinogenesis, oxidative stress

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Summya Rashid , Nemat Ali , Sana Nafees , Syed Kazim Hasan , Sarwat Sultana

Abstract

Objective: The present study was designed to investigate the chemo preventive efficacy of bee propolis (BP) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe‑NTA) promoted renal carcinogenesis in Wistar rats. Chronic treatment of Fe‑NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. BP is a resinous material collected by bees from various plants which has been used from centuries in folk medicine. Materials and Methods: Renal cancer was initiated by single intraperitoneal injection of N‑nitrosodiethylamine (DEN 200 mg/kg body weight) and promoted by twice weekly administration of Fe‑NTA 9 mg Fe/kg body weight for 16 weeks. The chemo preventive efficacy of BP was studied in terms of lipid peroxidation (LPO), renal anti‑oxidant armory such as catalase, superoxide dismustase, glutathione S‑transferase, glutathione peroxidase, glutathione reductase and glutathione (GSH), serum toxicity markers, cell proliferation, tumor suppressor protein and inflammation markers. Results: Administration of Fe‑NTA enhances renal LPO, with concomitant reduction in reduced GSH content and antioxidant enzymes. It induces serum toxicity markers, viz., blood urea nitrogen, creatinine and lactate dehydrogenase. Chemo preventive effects of BP were associated with upregulation of antioxidant armory and down regulation of serum toxicity markers. BP was also able to down regulate expression of proliferative cell nuclear antigen, cyclooxygenase‑2, tumor necrosis factor‑alpha and upregulated p53 along with induction of apoptosis. Histopathological changes further confirmed the biochemical and immunohistochemical results. Conclusion: These results provide a powerful evidence for the chemo preventive efficacy of BP against renal carcinogenesis possibly by modulation of multiple molecular pathways.

Keywords

Bee propolis, inflammation, oxidative stress, proliferation, renal carcinogenesis

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