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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Rashid Ali ¹, Shaheen Sultana ¹, Sarwat Sultana ², Amit Kumar ¹, Aseem Bhatnagar ¹, Gaurav Mittal ¹

Affiliations
1 Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, IN
2 Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, IN

Abstract

Alpha Ketoglutaric Acid (AKG), one of two ketone derivatives of glutaric acid is an important biological compound that serves as a natural scavenger of ammonium ion, facilitating its conversion to amino acids and protein. AKG inhalation has potential therapeutic role against ammonia-induced structural and inflammatory changes in the lungs. In the present study sub-acute inhalation toxicity of a novel submicronic AKG respiratory formulation was evaluated in Sprague Dawley rats. Sub-acute inhalation toxicity study of novel AKG respiratory formulation at doses, 1, 3 and 5% was conducted as per Schedule-'Y' guidelines of ICMR, India. Hematological, serum biochemical and lung toxicity biomarkers in bronchoalveolar lavage (BAL) fluid were determined. Histopathological analysis of lung tissues and other vital organs was carried out to observe any microscopic changes. Hematology, serum biochemistry and lung toxicity biomarkers in BAL fluid revealed no adverse effects of AKG inhalation except for a slight increase in levels of BAL fluid protein. At autopsy, no histopathological changes in major vital organs, including the lungs were observed. The safety evaluation data suggest that aerosols of submicronic AKG respiratory formulation are safe for inhalation and could be developed as a potential therapeutic option against lung injuries induced through chemical toxicants such as ammonia.

Keywords

Industrial Chemicals, Alpha-Ketoglutaric Acid, Sub-Micronic Aerosols, Inhalation Toxicity, BAL Fluid Analysis.

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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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Abdul Lateef , Muneeb U. Rehman , Mir Tahir , Rehan Khan , Abdul Quaiyoom Khan , Wajhul Qamar , Sarwat Sultana

Abstract

Background: In the present study, cigarette smoke contains more than four thousand chemicals, many of which are known to be carcinogen or cancer promoter. Many epidemiological reports suggest that cigarette smokers are at a greater risk of other cancers such as oropharynx, stomach, pancreas, liver, kidney, urinary bladder, colon, and breast, however, the few epidemiological reports are available on the role of cigarette smoke in the development of prostate cancer. In this study, we investigated the effects of farnesol against cigarette smoke extract (CSE)‑induced oxidative stress in prostate. Materials and Methods: Farnesol was administered by gavage (50 mg/kg and 100 mg/kg b.wt. in corn oil) one time daily for 7 days. On day 7, rats were exposed to cigarette smoke via intratracheal instillation of aqueous CSE. CSE enhanced prostatic xanthine oxidase activity and lipid peroxidation (LPO) along with decrease in prostatic glutathione content, antioxidant enzymes activities, viz., glutathione peroxidase, glutathione reductase, and catalase. Results: Pre‑treatment of rats with farnesol (50 mg/kg and 100 mg/kg b.wt. orally) resulted in significant decreased in xanthine oxidase activity and LPO at both the doses. The level of reduced glutathione, the activities of glutathione dependent enzymes and antioxidant enzymes were also augmented to significant level with pre‑treatment with farnesol. Conclusion: Thus, our data suggests that farnesol is a potent defense against CSE induced prostatic oxidative damage in rodent model of experiment.

Keywords

Cigarette smoke extract, farnesol, intratracheal instillation, prostate, testis

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Pooja Singh , K. Mathai Chacko , M. L. Aggarwal , Binu Bhat , R. K. Khandal , Sarwat Sultana , Binu T. Kuruvilla

Abstract

The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt.

Keywords

Boswellia serrata, NOAEL, safety, sub-chronic, toxicity, wistar rat

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