Rajesh Mandil

Differential modulation of xenobiotic-metabolizing enzymes in rats following single and concurrent exposure to chlorpyrifos, arsenic, and ascorbic acid.

The present study was undertaken to evaluate the subacute toxicity of arsenic (As) and chlorpyrifos (CPF) alone or in combination. In addition, the ameliorative effect of ascorbic acid on As and/or CPF-induced hepatic microsomal xenobiotic metabolizing enzymes in rats was examined. Rats were divided into 9 groups of 6 animals each: control (deionized water), vehicle control (groundnut oil), ascorbic acid (100 mg/kg body weight), As (40 ppm in water), CPF (5 mg/kg body weight), As (40 ppm) + CPF (5 mg/kg body weight), As + ascorbic acid, CPF + ascorbic acid, and As + CPF + ascorbic acid. After 28 d of exposure, rats were sacrificed and liver was extracted for isolation of hepatic microsomes. Exposure to As or CPF alone as well as both of these in combination significantly altered microsomal proteins and activity of phase I and phase II xenobiotic-metabolizing enzymes. Cytochrome P-450 and cytochrome b 5 levels and activities of aniline p-hydroxylase (APH) and uridine diphosphate glucuronosyltransferase (UGT) were significantly decreased in groups treated with As, CPF, and As plus CPF, while glutathione S-transferase (GST) was not markedly altered. Enzymatic activity of aminopyrine N-demethylase (ANDM) was also significantly reduced in As- and CPF-only groups. Co-administration of ascorbic acid effectively countered the As- and CPF-induced alterations in xenobiotic-metabolizing enzymes.

Environmental Attributes to Respiratory Diseases of Small Ruminants

Respiratory diseases are the major disease crisis in small ruminants. A number of pathogenic microorganisms have been implicated in the development of respiratory disease but the importance of environmental factors in the initiation and progress of disease can never be overemphasized. They irritate the respiratory tree producing stress in the microenvironment causing a decline in the immune status of the small ruminants and thereby assisting bacterial, viral, and parasitic infections to break down the tissue defense barriers. Environmental pollutants cause acute or chronic reactions as they deposit on the alveolar surface which are characterized by inflammation or fibrosis and the formation of transitory or persistent tissue manifestation. Some of the effects of exposures may be immediate, whereas others may not be evident for many decades. Although the disease development can be portrayed as three sets of two-way communications (pathogen-environment, host-environment, and host-pathogen), the interactions are highly variable. Moreover, the environmental scenario is never static; new compounds are introduced daily making a precise evaluation of the disease burden almost impossible. The present review presents a detailed overview of these interactions and the ultimate effect on the respiratory health of sheep and goat.

Curcumin attenuates oxidative stress-induced altered histoarchitecture of testes in experimentally exposed rats to metal mixture (lead, arsenic, cadmium, mercury, iron, and copper) for 28 days

This study was undertaken to assess the toxicity of mixture of six metals including lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), iron (Fe), and copper (Cu) at environmentally realistic concentrations and to determine whether curcumin was able to prevent testicular injury in rats. Forty-two rats were divided into seven groups, six animals/group: control (water), vehicle control (groundnut oil), curcumin (100 mg/kg body wt.), 10x mixture, 100x mixture, 10x plus curcumin, and 100x plus curcumin. At the end of exposure period of 28 days, rats were sacrificed and testes were collected for the analysis of oxidative stress markers, testicular enzymes, and histopathology. At 10x and 100x dose, % weight gain was significantly reduced compared to control, accompanied by decreased absolute testicular weight in 100x mixture group; however, relative weight among groups did not show any significant difference. Exposure of 10x and 100x mixture elevated the levels of lipid peroxidation products; whereas, catalase activity was significantly lowered. Glutathione content and superoxide dismutase activity were almost comparable among groups. Significant decrease in 17-β-hydroxysteroid hydrogenase and acid phosphatase, increase in γ-glutamyl transferase activity at 100x exposure level was observed. Lactate dehydrogenase and sorbitol dehydrogenase activity was comparable amongst all groups. Histopathological examination revealed degenerative changes in seminiferous tubules and spermatogonial cells. Co-administration of curcumin with metallic mixture effectively countered 10x and 100x metal mixtures-induced oxidative stress and improved antioxidant status of the tissue and restored activities of testicular enzymes. In conclusion, evidence indicates that major action of metals in testicular degeneration may be oxidative stress.

Eucalyptus robusta leaves methanolic extract suppresses inflammatory mediators by specifically targeting TLR4/TLR9, MPO, COX2, iNOS and inflammatory cytokines in experimentally-induced endometritis in rats

ETHNOPHARMACOLOGICAL RELEVANCE Bacterial endometritis is one of the major causes of reproductive disorders including infertility in farm animals. Antibiotics are generally used for treatment of such disorders but now a days residues of antibiotics are of great public health concern, therefore, phytoremediation is being considered as an alternative to use of antibiotics. AIM OF THE STUDY Present study was undertaken to investigate the efficacy of Eucalyptus robusta leaves methanolic extract against endometritis along with the possible mechanism of action especially targeting inflammatory biomarkers. MATERIALS AND METHODS Bacterial endometritis was produced using clinical isolates of E. coli and Staphyloccocus aureus from bovines (cows and buffaloes) endometritis cases. After seven days of inoculation of the mixed bacterial culture, endometritis was confirmed based on the presence of visible pus and edema, thinning of endometrial lining and presence of large number of polymorphonuclear cells and bacterial load in uterine flushing. Female Wistar rats were divided in to five groups namely control, sham-operated, endometritis, endometritis plus Eucalyptus leaves extract and endometritis plus cefixime. Serum specific inflammatory biomarkers (interleukin-1β, interleukin-10, tumor necrosis factor-α, intercellular adhesion molecule-1, serum amyloid A) and myleoperoxidase, toll like receptors-4 and -9, inducible nitric oxide synthase, nitric oxide, cyclooxygenase 1 and 2 were estimated in uterine tissues using ELISA kits. RESULTS Interleukin-10, serum amyloid A, myleoperoxidase, toll like receptors-4 and-9, cyclooxygenase-2, inducible nitric oxide synthase and nitric oxide were significantly increased while non significant increase in interleukin-1β, cycloxygenase-1 and intercellular adhesion molecule-1 were observed but level of tumor necrosis factor-α was found decreased in rats of endometritis group. Histopathological lesions in uterus showed efficient induction of endometritis by presence of inflammatory cells which are lessened effectively after treatment with Eucalyptus leaves extract. Eucalyptus robusta leaves extract produced curative and protective effect against endometritis and results were comparable to or even better than cefixime. CONCLUSIONS Eucalyptus robusta leaves extract possess promising antibacterial activity and efficacy against experimental endometritis and, therefore, holds promising potential for development of effective formulation for treatment of endometritis in animals.

In vivo antioxidant potential of ascorbic acid against lead and/or cypermethrin-induced oxidative tissue damage

Cypermethrin (CPM) and lead (Pb) are common environmental pollutants found in ecosystems. In the present study, levels of oxidative stress generated were investigated in the liver, kidney and spleen of female Wistar rats after a 28-day exposure to CPM and Pb, alone or in combination, in presence or absence of ascorbic acid as a prophylactic antioxidant treatment. The significant decline in protein content of liver was observed in CPM or Pb alone as well as co-exposed groups. Both CPM and Pb were found to be potent inducers of oxidative stress. Significant increase in lipid peroxidation (LPO) and decrease in glutathione (GSH) levels were noted in all the tissues examined. Glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities were significantly lowered in spleen while superoxide dismutase (SOD) showed marked fall in liver and spleen. Oxidative stress was reduced in the co-exposure group as compared to CPM or Pb alone treated groups. Ascorbic acid exhibited considerable restorative effects against Pb, CPM alone or in combination as revealed by significant return of values of LPO, CAT, SOD and GPx to control. The improved antioxidant status of liver, kidney and spleen by ascorbic acid may represent a promising tool for chemoprevention against heavy metal and/or pesticide toxicity in humans and animals. Further studies are required to unravel the molecular mechanistic underlying toxicological implications of metal pesticide binary mixture toxicity.

Antioxidant role of ascorbic acid on oxidative stress induced by sub-acute exposure of lead and cypermethrin in erythrocytes of Wistar rats

This study aimed to evaluate the reparative potential of ascorbic acid (AA, 100 mg/kg, orally for 28 days) in sub-acute lead (Pb, 100 ppm in drinking water for 28 days) or cypermethrin (CPM, 50 mg/kg, orally in vehicle for 28 days) poisoning alone and as binary mixture on the basis of oxidative stress parameters in erythrocytes of Wistar rats. Both Pb and CPM produced significant increase in lipid peroxidation along with elevated glutathione-S-transferase and catalase activity individually but not as a binary mixture. Glutathione peroxidase activity was significantly increased but glutathione levels were significantly reduced irrespective of single or co-exposure while the activity of superoxide dismutase and erythrocytic protein content were not significantly affected. Co-exposure led to a comparatively lower level of oxidative stress than that induced by Pb or CPM alone indicating an antagonistic toxicodynamic profile in rat erythrocytes. Co-administration of AA along with Pb and/or CPM significantly restored the oxidative stress parameters to normal values. Overall results indicated that co-exposure induces a lower level of oxidative stress and AA ameliorates Pb- and/or CPM-induced oxidative damage in rat erythrocytes.