Tajdar Husain Khan

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.

Soy isoflavones inhibits the genotoxicity of benzo(a)pyrene in Swiss albino mice

Dietary factors are considered important environmental risk determinants for various diseases. Isoflavones are one of the biologically active polyphenolic plant constituents that possess potential chemopreventive properties against a wide variety of chronic diseases. In the present study we have evaluated the antimutagenic potential of soy isoflavones against benzo(a)pyrene (B[a]P) (125 mg/ kg) induced genotoxicity in Swiss albino mice. The effect of soy isoflavones was studied by in vivo bone marrow chromosomal aberration and micronuclei induction test. Using an alkaline unwinding assay we monitored the DNA strand breaks. Two doses of soy isoflavones (20 and 40 mg/kg b.wt) were given orally for seven days prior to the administration of B[a]P. Soy isoflavone inhibited the genotoxicity of B[a]P in terms of chromosomal aberration and micronucleus formation. DNA strand break levels in only B[a]P treated group remained significantly high f the control values (P <0.001). The pretreatment of soy isoflavone showed gradual reduction in strand breaks significantly (P <0.001) and dose dependently. Soy isoflavone pretreatment also decreased cytochrome P450 (CYP) content. The activity of CYP was also decreased dose dependently by pretreatment with soy isoflavone. The chemopreventive effect of soy isoflavone on the inhibition of CYP activity and DNA integrity mediate the possible mechanism of inhibition of genotoxicity.

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.

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.

Effect of Aegle marmelos on DEN initiated and 2-AAF promoted hepatocarcinogenesis: a chemopreventive study

In this study, we examined the inhibitory effects of Aegle marmelos methanolic extract on diethylnitrosamine (DEN) initiated and 2-acetyl aminofluorene (2-AAF) promoted liver carcinogenesis in male Wistar rats. Interestingly, it was found that A. marmelos (25 and 50 mg/kg body weight) resulted in a marked reduction of the incidence of liver tumors, which was further confirmed with histopathology. Furthermore to understand the underlying mechanisms of chemoprevention potential of A. marmelos, we evaluated the levels of hepatic antioxidant defence enzymes, ornithine decarboxylase (ODC) activity and hepatic DNA synthesis as a marker for tumor promotion since a direct correlation between these marker parameters and carcinogenicity have been well documented. Treatment of male Wistar rats for five consecutive days with 2-AAF induced significant hepatic toxicity, oxidative stress and hyper-proliferation. Pretreatment of A. marmelos extract (25 and 50 mg/kg body weight) prevented oxidative stress and toxicity by restoring the levels of antioxidant enzymes at both the doses. The promotion parameters (ODC activity and DNA synthesis) induced by 2-AAF administration in diet with partial hepatectomy (PH) were also significantly suppressed dose-dependently by A. marmelos. Therefore, we can conclude that ultimately the protection against liver carcinogenesis by A. marmelos methanolic extract might be mediated by multiple actions, which include restoration of cellular antioxidant enzymes, detoxifying enzymes, ODC activity and DNA synthesis.

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.

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats

Abstract Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. Results: CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.

Antioxidant potential of Rumex vesicarius L.: in vitro approach.

OBJECTIVE To assess in-vitro antioxidant activity of different fraction and perform high performance thin layer chromatography fingerprint analysis of most active fraction of Rumex vesicarius L. (R. vesicarius). METHODS In the present study, acetone, ethyl acetate, n-butanol, and methanol extracts of R. vesicarius were evaluated for radical scavenging activity by studying the inhibition of the level of lipid peroxidation induced by Fe(++)/ascorbate, DNA sugar damage, scavenging of hydrogen peroxide, diphenylphosphine DPPH radical scavenging activity, total phenolic content, total flavonoids content and total proanthocyanidin. High performance thin layer chromatography finger print profiling of R. vesicarius L. was also done. RESULTS Lipid peroxidation induced by the iron/ascorbate system, hydrogen peroxide, diphenylphosphine and DNA sugar damage were inhibited by the addition of different extract of R. vesicarius. Among them, methanolic extract showed maximum efficacy. The methanolic extract showed the highest total phenolic, total flavonoids and total proanthocyanidin contents. CONCLUSIONS The results suggest that the extracts can be a vital source of phytochemical antioxidants.