Tamanna Jahangir

Emblica officinalis and hepatocarcinogenesis: a chemopreventive study in Wistar rats.

INTRODUCTION Emblica officinalis L. commonly known as gooseberry, Phyllanthus emblica, Emblica, Indian gooseberry, amla is used in Indian system of medicine for the treatment of liver ailments. AIM AND OBJECTIVES In the present study, we report that it ameliorates the carcinogenic response as it reverses the histopathological changes and reduces the number of gamma-GT-positive foci induced by Solt Farber protocol in the liver of Wistar rats. MATERIALS AND METHODS Tumors were induced by initiation with diethylnitrosoamine (DEN) (200 mg/kg body wt., i.p.) followed by promotion with 2-acetylaminoflourine (2-AAF) (0.02%, w/w in diet) for continuous 6 weeks and the animals were subjected to partial hepatectomy on day 21 of initiation. RESULTS Pretreatment with defatted methanolic fruit extract (100 and 200mg/kg b.w.) of Emblica officinalis showed significant partial recovery of pathological manifestations as compared to DEN and 2-AAF-treated group animals (p<0.001) and suppressed the tumor forming potential of 2-AAF (p<0.05) at both the doses. CONCLUSION Emblica officinalis has the potential to suppress carcinogen-induced response in rat liver.

Emblica officinalis reverses thioacetamide‐induced oxidative stress and early promotional events of primary hepatocarcinogenesis

Emblica officinalis is widely used in Indian medicine for the treatment of various diseases. In the present study, it was found that fruits of E. officinalis inhibit thioacetamide‐induced oxidative stress and hyper‐proliferation in rat liver. The administration of a single necrotic dose of thioacetamide (6.6 mM kg−1) resulted in a significant (P< 0.001) increase in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and γ‐glutamyl transpeptidase (GGT) levels compared with saline‐treated control values. Thioacetamide caused hepatic glutathione (GSH) depletion and a concomitant increase in malanodialdehyde (MDA) content. It also resulted in an increase (P< 0.001) in the activity of glutathione‐S‐transferase (GST), glutathione reductase (GR), glucose 6‐phosphate dehydrogenase (G6PD) and a decrease in glutathione peroxidase (GPx) activity (P< 0.001). Hepatic ornithine decarboxylase activity and thymidine incorporation in DNA were increased by thioacetamide administration. Prophylactic treatment with E. officinalis for 7 consecutive days before thioacetamide administration inhibited SGOT, SGPT and GGT release in serum compared with treated control values. It also modulated the hepatic GSH content and MDA formation. The plant extract caused a marked reduction in levels of GSH content and simultaneous inhibition of MDA formation. E. officinalis also caused a reduction in the activity of GST, GR and G6PD. GPx activity was increased after treatment with the plant extract at doses of 100 mg kg−1 and 200 mg kg−1. Prophylactic treatment with the plant caused a significant down‐regulation of ornithine decarboxylase activity (P< 0.001) and profound inhibition in the rate of DNA synthesis (P< 0.001). In conclusion, the acute effects of thioacetamide in rat liver can be prevented by pre‐treatment with E. officinalis extract.

Inhibitory effect of apigenin on benzo(a)pyrene‐mediated genotoxicity in Swiss albino mice

Apigenin, a bioflavonoid, is abundantly present in fruits and vegetables and possesses potential chemopreventive properties against a wide variety of chronic diseases. In this study we investigated the anti‐genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg kg−1 orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P‐450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg kg−1 orally) dose dependently (P < 0.001). B(a)P‐induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione‐S‐transferase (GST) was also shown to be restored by apigenin pre‐treatment (P < 0.001). A simultaneous significant and dose‐dependent reduction was noted in DNA strand breaks and in‐vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P‐induced toxicity.

Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats

Excess iron deposition in tissues leads to organ dysfunction and impairment. In this study, the protective effects of farnesol (FL), an isoprenoid, against Fe-NTA (9 mg iron/kg body weight i.p.)-induced oxidative damage and early tumour promotion markers are evaluated. The pretreatment of iron-intoxicated rats with 1% and 2%/kg body weight oral dose of FL for 7 consecutive days significantly reversed the iron-induced increase in H2O2 content (P <0.001), malondialdehyde formation, xanthine oxidase activity (P <0.001), ornithine decarboxylase activity (P <0.001) and 3[H]thymidine incorporation in renal DNA (P <0.005) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen (BUN) and creatinine (P <0.001). Significant dose-dependent restoration was recorded in renal glutathione content, its dependent enzymes and other phase II metabolizing enzymes viz., catalase, glutathione-S-transferase and quinone reductase (P <0.001) with prophylactic treatment of FL. Present results support that FL markedly lowers the oxidative damage and appearance of tumour markers, which precludes its development as a chemopreventive tool.

Pluchea lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity in Swiss albino mice.

Cadmium intoxication induces lipid peroxidation and causes oxidative damage to various tissues by altering antioxidant defence system enzymes. At 24h after treatment with a single intraperitoneal dose of cadmium chloride (5 mg kg−1), Swiss albino mice showed a significant increase in the levels of malanodialdehyde and xanthine oxidase (P<0.001), and a concomitant depletion of renal glutathione, catalase (P<0.001) and other antioxidant enzymes. CdCl2 also led to a simultaneous increase in micronuclei formation (P<0.001) and chromosomal aberrations (P<0.05) in mouse bone marrow cells. Oral pre‐treatment with Pluchea lanceolata extract at doses of 100 and 200 mg kg−1 for 7 consecutive days before CdCl2 intoxication caused a significant reduction in malanodialdehyde formation and xanthine oxidase activity (P<0.001). A significant restoration of the activity of antioxidant defence system enzymes such as catalase, glutathione peroxidase (P<0.05), glutathione‐S‐transferase and glutathione reductase (P<0.001) was observed. A significant dose‐dependent decrease in chromosomal aberrations and micronuclei formation was also observed (P<0.05). The results indicate that pre‐treatment with P. lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity by altering antioxidant enzymes and reducing chromatid breaks and micronuclei formation.

Perillyl Alcohol Protects against Fe-NTA-Induced Nephrotoxicity and Early Tumor Promotional Events in Rat Experimental Model

Plants have been widely used as protective agents against a wide variety of processes and compounds that damage tissues via free radical mechanisms. Perillyl alcohol (PA) is a naturally occurring monoterpene found in the essential oils of numerous species of plants including mints, cherries and celery seeds. This monocyclic monoterpene has shown antioxidant and therapeutic activity in various studies against various xenobiotics. In this study, we have analyzed the effects of PA against single intraperitoneal dose of ferric nitrilotriacetate (Fe-NTA) (9 mg iron per kg body weight)-induced nephrotoxicity and early tumor promotional events. The pretreatment of Fe-NTA-treated rats with 0.5% per kg body weight dose and 1% per kg body weight dose of PA for seven consecutive days significantly reversed the Fe-NTA-induced malondialdehyde formation, xanthine oxidase activity (P < 0.001), ornithine decarboxylase activity (P < 0.001) and 3[H]thymidine incorporation in renal DNA (P < 0.001) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen and creatinine (P < 0.001). Significant restoration at both the doses was recorded in depleted renal glutathione content, and its dependent enzymes with prophylactic treatment of PA. Present results suggest that PA potentially attenuates against Fe-NTA-induced oxidative damage and tumor promotional events that preclude its development as a future drug to avert the free radical-induced toxicity.

Effect of gallic acid on renal biochemical alterations in male Wistar rats induced by ferric nitriloacetic acid

The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress and cell proliferation plays an important causative role. This study was designed to investigate the effect of gallic acid against ferric nitrilotriacetic acid (Fe-NTA)-induced carcinogen/drug metabolizing phase I and phase II enzymes, anti-oxidative parameters, kidney markers, tumour promotion markers and lipid peroxidation (LPO) in kidney of male Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) caused significant depletion in the detoxification and antioxidant enzyme armoury with concomitant elevation in renal LPO, serum creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine decarboxylase activity and [3H]thymidine incorporation into renal DNA. However, pretreatment of animals with gallic acid (10 and 20 mg/kg body weight) resulted in a significant decrease in the levels of the parameters measured (P < 0.001). Renal glutathione content (P < 0.001), glutathione metabolizing enzyme (P < 0.001) and antioxidant enzyme levels were also recovered to a significant level (P < 0.001). The enhanced reduced glutathione level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of gallic acid against Fe-NTA-mediated oxidative stress, toxicity and cell proliferative response in Wistar rats.

Reversal of Cadmium Chloride-Induced Oxidative Stress and Genotoxicity by Adhatoda vasica Extract in Swiss Albino Mice

Adhatoda vasica Nees (Acanthaceae) that is used by Ayurvedic physicians possesses some established medicinal properties. Environmental and occupational exposure with cadmium affects the renal system adversely. Cadmium is an established genotoxic agent. In the present study, we evaluated the antioxidant and anticlastogenic efficacy of A. vasica against cadmium chloride (CdCl2)-induced renal oxidative stress and genotoxicity in Swiss albino mice. A single intraperitoneal dose of CdCl2 (5 mg/kg BW) resulted in significant (p<0.001) increase in chromosomal aberration and micronuclei formation. Oral administration of A. vasica at two doses (50 and 100 mg/kg BW) for seven consecutive days showed significant (p<0.001) suppression of mutagenic effects of CdCl2 in plant-pretreated groups. To study the mechanism by which A. vasica exerts its antimutagenic potential, enzymes involved in metabolism and detoxification were also estimated. Cadmium intoxication altered the antioxidant levels and enhanced MDA formation significantly (p<0.001). A. vasica showed significant (p<0.001) recovery in antioxidant status, viz., GSH content, its dependent enzymes, and catalase activity. Prophylactic pretreatment of A. vasica extract in cadmium-intoxicated mice showed marked (p<0.001) inhibition of lipid peroxidation (LPO) and xanthine oxidase (XO) activity. The present findings support that antimutagenic efficacy of A. vasica can be attributed to its restoring effects on antioxidant status and suppression of MDA level formation.

Modulatory effects of Pluchea lanceolata against chemically induced oxidative damage, hyperproliferation and two-stage renal carcinogenesis in Wistar rats

Ferric nitrilotriacetate (Fe-NTA) is a well-established renal carcinogen. Here, we have shown that Pluchea lanceolata (PL) belonging to the family Asteraceae. PL attenuates Fe-NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. It promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) and renal DNA synthesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) also enhances renal lipid peroxidation (LPO), xanthine oxidase (XO) and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content (GSH), antioxidant enzymes, viz., glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase (QR). It also enhances blood urea nitrogen (BUN) and serum creatinine. Oral treatment of rats with PL extract (100 and 200 mg/kg body weight) resulted in significant decrease in lipid peroxidation (LPO), xanthine oxidase (XO), H2O2 generation, blood urea nitrogen (BUN), serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), its metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, present study supports PL as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rat.

Acorus calamus extracts and nickel chloride : Prevention of oxidative damage and hyperproliferation response in rat kidney

Nickel, a major environmental pollutant, is known for its clastogenic, toxic, and carcinogenic potential. In this article, we report the effect of Acorus calamus on nickel chloride (NiCl2)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl2 (250 μmol/kg body weight/mL) enhanced reduced renal glutathione content (GSH) glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H2O2 generation, blood urea nitrogen (BUN), and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (GPx) (p<0.001). NiCl2 administration also dose-dependently induced the renal ornithine decarboxylase (ODC) activity several-fold as compared to salinetreated control rats. Similarly, renal DNA synthesis, which is measured in terms of [3H] thymidine incorporation in DNA, was elevated following NiCl2 treatment. Prophylactic treatment of rats with A. calamus (100 and 200 mg/kg body weight po) daily for 1 wk resulted in the diminution of NiCl2-mediated damage, as evident from the downregulation of glutathione content, GST, GR, LPO, H2O2 generation, BUN, serum creatinine, DNA synthesis (p<0.001), and ODC activity (p<0.01) with concomitant restoration of GPx activity. These results clearly demonstrate the role of oxidative stress and its relation to renal disfunctioning and suggest a protective effect of A. calamus on NiCl2-induced nephrotoxicity in a rat experimental model.