Aswin M. Thaker

Hematological and biochemical changes due to short-term oral administration of imidacloprid

Subacute toxicity of repeated (28 day) oral administration of imidacloprid in male White Leghorn (WLH) chicks was assessed. One hundred and twenty-five birds were divided into five groups, with each group containing 25 birds. The birds of group C1 were given no treatment and served as control. Group C2 was administered groundnut oil (1 ml/kg) and served as control (vehicle). Group I1 was given 1/40 th of apparent LD 50 (ALD 50 ) (1.25 mg/kg), and group I2 was put on 1/30 th of ALD 50 (1.67 mg/kg), while group I3 received 1/20 th of ALD 50 (2.5 mg/kg) of imidacloprid suspended in groundnut oil. The blood samples were collected from birds after 14 and 28 days of oral administration and analyzed for hematological and biochemical parameters. The study showed that hematological parameters [hemoglobin (Hb), packed cell volume (PCV), total erythrocyte count (TEC)] remained unaffected except total leukocyte count which was decreased at the highest dose tested only on 28 th day of experiment in birds of group I3. Imidacloprid produced hypoglycemia during the entire period of study, which was dose dependent. Imidacloprid treated birds showed significant increase in serum glutamate oxaloacetate transaminase (SGOT) level at 14 and 28 days of experiment, while no significant change in serum glutamate pyruvate transaminase (SGPT), serum total protein, serum total albumin, serum total globulin and serum creatinine was seen.

The effects of adenosine A2B receptor inhibition on VEGF and nitric oxide axis-mediated renal function in diabetic nephropathy

Abstract Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. The pathophysiologic mechanisms of diabetic nephropathy are incompletely understood but include overproduction of various growth factors and cytokines. Upregulation of vascular endothelial growth factor (VEGF) is a pathogenic event occurring in most forms of podocytopathy; however, the mechanisms that regulate this growth factor induction are not clearly identified. A2B receptors have been found to regulate VEGF expression under hypoxic environment in different tissues. One proposed hypothesis in mediating diabetic nephropathy is the modulation of VEGF-NO balance in renal tissue. We determined the role of adenosine A2B receptor in mediating VEGF overproduction and nitrite in diabetic nephropathy. The renal content of A2B receptors and VEGF was increased after 8 weeks of diabetes induction. The renal and plasma nitrite levels were also reduced in these animals. In vivo administration of A2B adenosine receptor antagonist (MRS1754) inhibited the renal over expression of VEGF and adverse renal function parameters. The antagonist administration also improved the kidney tissue nitrite levels. In conclusion, we demonstrated that VEGF induction via adenosine signaling might be the critical event in regulating VEGF-NO axis in diabetic nephropathy.

The effects of A2B receptor modulators on vascular endothelial growth factor and nitric oxide axis in chronic cyclosporine nephropathy.

Introduction: To investigate the actions of adenosine A2B receptor modulators on VEGF and NO levels in CsA nephropathy. Materials and Methods: Nephropathy was induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO levels were measured in kidney tissue. Serum creatinine, creatinine clearance, urinary albumin excretion, blood urea nitrogen, kidney pathology score were measured to assess renal function. The analysis of mRNA expression of A2B receptor and VEGF was performed. Results: Administration of CsA for 5 weeks induced adverse renal function. The mRNA expression of VEGF was reduced in renal tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also reduced in these animals. In vivo administration of A2B adenosine receptor agonist increased renal VEGF which was inhibited by a selective A2BAR antagonist (MRS1754) in CsA-treated animals. The increase in VEGF was associated with reversal of adverse renal functions. The effects of A2BAR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A2BARs. The mRNA expression of A2BAR was increased after 5 weeks of CsA. Conclusions: A2BAR modulators may provide new therapeutic options to retard CsA nephropathy by mediating renal VEGF and NO.

Evaluation of antigout activity of Phyllanthus emblica fruit extracts on potassium oxonate-induced gout rat model

Aim: The present study has been conducted to evaluate antigout activity of aqueous and alcoholic extracts of Phyllanthus emblica fruits following its 28 days repeated oral administration on potassium oxonate-induced gout rat model. Materials and Methods: The study was conducted on 42 male Sprague-Dawely rats dividing them in seven groups having six rats in each group. Groups I, II, and III served as vehicle control group, gout control group, and standard treatment control group, respectively. Rats of all the groups except vehicle control group were administered potassium oxonate at 250 mg/kg (IP), throughout the study period (28 days) for induction of gout. Groups IV and V received aqueous extract of P. emblica at 200 and 400 mg/kg, and Groups VI and VII received alcoholic extract of P. emblica at 200 and 400 mg/kg (daily oral for 28 days). At the end of study, all the rats were subjected to blood collection; blood and serum sample were analyzed for hematological and biochemical parameters, respectively. After collection of blood samples on the 29th day, all the rats were sacrificed and subjected to post mortem examination to determine the presence or absence of gross and histopathological lesions in kidney tissues. Results: At the end of study, rats of gout control group showed increase in platelets counts, serum creatinine, uric acid, blood urea nitrogen (BUN), and xanthine oxidase (XO) enzyme level along with alterations in kidney tissues as compared to vehicle control group. Gouty rats treated with aqueous and alcoholic extracts of P. emblica at 200 and 400 mg/kg body weight and standard treatment allopurinol at 5 mg/kg body weight showed reduction in platelets counts, serum creatinine, uric acid, BUN, and XO enzyme level along with significant improvements in histological structure of kidney as compared to rats of gout control group. Conclusion: Oral administration of aqueous and alcoholic extracts of P. emblica fruits for 28 days has shown protection against gout in dose-dependent manner in rats.

Acephate immunotoxicity in White Leghorn cockerel chicks upon experimental exposure

Immunotoxicity for subacute exposure to acephate (O,S-dimethyl-acetylphosphoramidothioate) was assessed in day old White Leghorn (WLH) cockerel chicks. The chicks were divided into five groups. Groups C1 and C2 served as plain control and vehicle control respectively. Chicks of groups T1, T2 and T3 were administered acephate suspended in groundnut oil at 21.3mg/kg, 28.4mg/kg and 42.6mg/kg respectively orally for 28 days. A non-significant reduction in total leukocyte count was observed. Although, anti-Newcastle Disease Virus (NDV) antibody titer, serum total protein (TP), serum globulin, serum albumin and organ:body weight ratios of immune organs were significantly suppressed. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene (DNCB) was not significantly altered. Histopathologically, bursa and spleen showed mild depletion of lymphocytes. Furthermore, DNA fragmentation assay was performed and detected ladder pattern (180bp) in DNA. It was concluded that subacute acephate exposure at low concentrations may affect immune responses in avian species.

Hematological and Immunological Changes Due to Short-term Oral Administration of Acephate.

To evaluate immunotoxicological effects of environmental chemical, subacute toxicity of repeated (28 day) oral administration of acephate (Ace) in BALB/c mice was assessed. Thirty two (sixteen male and sixteen female) mice were divided into four different groups with each group containing eight (four male and four female) mice. Mice of Group C1 were administered normal saline only and served as control. Group T1 was given 1/40 th of apparent LD 50 (ALD 50 ) (8.78 mg/kg), and group T2 was put on 1/30 th of ALD 50 [11.7 mg/kg], while group T3 received 1/20 th of ALD 50 [17.55 mg/kg] of Ace suspended in normal saline. The blood samples were collected from mice after 28 days of oral administration and analyzed for hematological, biochemical, and immunological parameters. The study showed that hematological parameters (monocytes and granulocytes) remained unaffected except total leukocyte count and lymphocyte which were decreased highly significantly [ P≤0.01] in mice of group T3 on the 28 th day of experiment. Serum total protein (TP) and serum globulin decreased significantly in mice of treatment groups dose dependently; however, no significant change was seen in serum albumin. Progressive increase in live body weight of mice decreased significantly in extremely toxic group only while spleen:body weight ratio decreased significantly in dose-dependent manner. Furthermore, Ace produced suppressed humoral immune response and the delayed-type hypersensitivity response to Sheep red blood cells (SRBCs) was altered nonsignificantly. The results of this study describe the suppression of immune responses following exposure to Ace at low concentrations in experimental mice.

Chapter 51 – Shilajit

Shilajit is a widely used natural herbo-mineral in Ayurveda, the traditional Indian system of medicine. It is a sticky brown to blackish physiologically active organic matter exuded from steep rocks in many mountain ranges of the world, especially the Himalayas of the Indian subcontinent. Shilajit is composed of humus and organic plant material, and its active constituents include dibenzo-alpha-pyrones, dibenzo-alpha-pyrone-chromoproteins, and fulvic acids. It exhibits antioxidant, immunomodulatory, anti-inflammatory, adaptogenic, and antidyslipidemic activities. It has cholinergic and parasympathomimetic effects. Studies conducted in animal models tend to support its use as a “revitalizer,” enhancing physical performance and relief from fatigue with enhanced ATP production. Further systematic research is needed to elucidate the exact mechanism of action of shilajit as a rejuvenator. Studies involving animals and humans indicate that the use of shilajit may be safe and free from adverse effects. Additional well-controlled studies on standardized products are needed in humans and animals.