Lakshmi Prasad

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.

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.

Modulatory effect of Morus indica against two-stage skin carcinogenesis in Swiss albino mice: possible mechanism by inhibiting aryl hydrocarbon hydroxylase

The modulatory effect of the methanolic extract of Morus indica on 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) induced oxidative stress and 7,12‐dimethylbenz(a)anthracene induced and croton oil (0.5% per mouse/0.2 mL acetone, v/v) promoted skin tumourigenesis in Swiss albino mice was studied. The efficacy of the M. indica extract was also evaluated in‐vitro by studying the inhibition of the activity and level of aryl hydrocarbon hydroxylase, cytochrome P450, DNA sugar damage in calf thymus DNA and Fe++/ascorbate‐induced lipid peroxidation in microsomes of mice. Significant increases in the activity of antioxidant enzymes (P < 0.001) and a concomitant decrease (P < 0.001) in the cutaneous malondialdehyde level were observed at three doses of plant extract (2.5, 5.0 and 7.5 mg kg−1). Application of M. indica 1 h before each application of croton oil showed inhibitory effects on tumour promotion in terms of a reduction in the number of tumours/mouse and percentage of mice with tumours. It was also accompanied by an extension of the tumour latency period. TPA, which resulted in a rapid and transient stimulation of mouse epidermal ornithine decarboxylase activity (P < 0.001), was inhibited dose dependently by pre‐treatment with M. indica extract (P < 0.001). The results suggest that M. indica extract may be useful as a therapeutic agent for cancer control as it blocks or suppresses events associated with chemical carcinogenesis.

Effect of Luteolin on Nickel Chloride-Induced Renal Hyperproliferation and Biotransformation Parameters in Wistar Rats

Abstract Nickel, a major environmental pollutant, is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of luteolin on nickel chloride (NiCl2)-induced renal oxidative stress, toxicity, and cell proliferation response in male Wistar rats. NiCl2 (250 µmol/kg b.wt./2 mL) enhances 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 compared with the activity in saline-treated rats. Similarly, renal DNA synthesis, which is measured as [3H]thymidine incorporation in DNA, is also increased after NiCl2 treatment. Prophylactic treatment of rats with luteolin (10 and 20 µmol/kg b.wt.) daily for 1 week 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. Thus, the current investigation suggests that luteolin can be used as a chemopreventive agent for cancer prevention as evident from the study where it blocks or suppresses the events associated with chemical carcinogenesis.