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2018 - 201912020 - 20221
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Subject: Veterinary Pharmacology and Toxicology × Author: Verma, Manish Kumar × Start date: 2015 × Type: Thesis ×
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    ThesisItemOpen Access
    Evaluation of therapeutic efficacy of Amaranthus hypochondriacus seed extract in fipronil intoxicated rats with special reference to In Silico prediction of squalene-CYP3A1 gene interaction
    (G.B. Pant University of Agriculture and Technology, Pantnagar, District Udham Singh Nagar, Uttarakhand. PIN - 263145, 2022-08) Verma, Manish Kumar; Singh, S.P.
    This study was designed to evaluate the protective efficacy of Amaranthus hypochondriacus seed extract (HSEAH) following its oral administration @ 100 mg/kg b. wt. alone and simultaneously with fipronil @ 24.25 mg/kg b. wt. orally for 90 days in rats by measuring haematobiochemical, oxidative, reproductive, histopathological examination, impact on gene expression of CYP3A1 and residue analysis parameters. Hydroethanolic extract of the seed of Amaranthus hypochondriacus was prepared for phytochemical analysis and in vitro evaluation of antioxidant potential was undertaken in-silico prediction of squalene-CYP3A1 gene interaction. Phytochemical analysis revealed the presence of various phytochemical like alkaloid, flavonoids, carbohydrates, proteins, glycosides, oils, phenolic compounds, terpenoids, saponins and tannins whereas the coumarins, resins and steroids were absent. Mineral estimation reveled presence of calcium, iron magnesium, zinc, and copper was present in higher concentration whereas lead, cobalt and nickel in trace amount. In-silico study of cross linking comparison between squalene and fipronil-CYP3A1 gene interaction was found to have high binding affinities for squalene than fipronil. In vitro antioxidant activity assessed by measuring NO radical scavenging, DPPH radical scavenging, reducing power activity, and metal chelating of Fe+2 activities which revealed the excellent antioxidant potential of extract. For evaluation of protective efficacy of HSEAH in fipronil intoxicated rats, twenty four male Wistar rats weighing 90-100 gm of 4-6 weeks of age were divided equally and randomly into four groups. Group I served as control, in group II fipronil @24.25 mg/kg b. wt. po, in group III HSEAH @ 100 mg/kg b wt. po, and in group IV HSEAH 100 mg/kg b. wt. plus fipronil @24.25 mg/kg b. wt. po., were given for 90 days. The reduction in body weight and organ weight significantly decreased in fipronil group. However, reduction in body weight was restored in HSEAH treated group IV. Fipronil exposure caused significant (P<0.05) reduction in Hb, PCV, MCV, MCH, MCHC, TLC and DLC as compared to control groups. A significant (P<0.05) decline in total protein, albumin and globulin was observed in group II as compared to control. Fipronil plus HSEAH treated group IV showed significant (P<0.05) amelioration in the level of total proteins as compared to group II and at par with normal values in control showing ameliorative effect of HSEAH. A significant (P<0.05) increase in AST, ALT, ALP, LDH, glucose, creatinine, BUN, cholesterol, triglycerides and LDL were significant decreased in fipronil treated group II, which were restored by HSEAH towards normalcy indicating amelioration of these parameters by HSEAH. A significant (P<0.05) decline in catalase, GSH and SOD and an increase in LPO in RBCs and tissues was observed in group II which, however, returned to normalcy following simultaneous administration of HSEAH in group IV after 90 days. Administration of HSEAH alone in group III significantly elevated the catalase, GSH and SOD activity as compared to control group I. Histopathological changes were observed in liver, kidney, lungs, spleen, heart, intestine, testis, brain and thyroid fipronil treated rats which were ameliorated by treatment with HSEAH after 90 days in rats. Gene expression study revealed that expression of CYP3A1 gene was upregulated in fipronil treated rats and down regulated in group IV treated with fipronil plus seed extract as compared to animals of control group I. A significantly (P<0.05) high sperm morphological abnormalities and decrease in sperm motility, sperm viability, and sperm density was observed group II rat whereas, treatment with HSEAH restored these parameters towards normal values. A comparison of tissue residue study in between fipronil alone and combination with HSEAH, detected significantly (P<0.05) higher fipronil residues in the tissues of group II in comparison with group IV rats indicating ameliorating efficacy of HSEAH. It is concluded from this study that the extract of HSEAH exhibited the antioxidant property. Administration of fipronil @24.25 mg/kg b.wt. po, produced haemotoxic, hepatotoxic, nephrotoxic, cardiotoxic, reproductive toxic and oxidative, which were ameliorated following simultaneous administration of Amaranthus hypochondriacus seed extract @ 100 mg/kg b. wt. po, for 90 days in rats.
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    ThesisItemOpen Access
    Evaluation of immunomodulatory and hepatoprotective potential of Chenopodium album Linn. in rats
    (G.B. Pant University of Agriculture and Technology, Pantnagar - 263145 (Uttarakhand), 2018-06) Verma, Manish Kumar; Ahmad, A.H.
    The present study was carried out to investigate the ameliorating potential of Chenopodium album Linn. in combating cyclophosphamide induced immunosuppression. The phytochemical analysis of plant extract revealed the presence of alkaloids, flavonoids, saponins, phenolic compounds, reducing sugars, glycosides and proteins. The experimental designs compromised of eight groups with each group having six rats. Group I served as control, group II rats were administered cyclophosphamide @100 mg/kg b. wt. in group III levamisole was administered @ 50 mg/kg b wt. in group IV both cyclophosphamide and levamisole, group V and VI were administered hydroethanolic extract of Chenopodium album (CAHE) @ 200 and 400 mg/kg b. wt. respectively, and in group VII and VIII CAHE @ 200 and 400 mg/kg b. wt. was given along with cyclophosphamide @100mg/kg b wt. on 9th and 16th day of study respectively, for 28 days. The reduction in body weight and organ weight significantly decreased in cyclophosphamide group. However, reduction in body weight was restored in group VII and VIII. Cyclophosphamide exposure caused significant (P<0.05) reduction in Hb, PCV, MCV, MCH, MCHC, TLC and DLC as compared to other groups. A significant (P<0.05) decline in total protein, albumin, globulin and A: G was observed in group II as compared to control. CAHE treated groups V, VI, VII and VIII showed significant (P<0.05) amelioration in the level total proteins as compared to group II and at par with normal values in control showing ameliorative effect of CAHE. A significant (P<0.05) increase in triglycerides, cholesterol, creatinine, BUN, AST, ALT and ALP was observed in cyclophosphamide treated group II, which were restored by CAHE towards normal indicating amelioration of these parameters by CAHE. A significant (P<0.05) decrease in HA titre, total Ig level, DTH reaction, phagocytic index, neutrophil adhesion and immunoglobulin (IgM and IgG) was observed in cyclophosphamide treated group II, whereas, treatment with CAHE restored these parameters towards normal values in a dose dependent manner indicating immune stimulation by CAHE. Histopathological changes in liver were characterized by severe congestion of blood vessels, Kupffer cell proliferation, severe sinusoidal congestion leading to loss of sinusoidal spaces, accumulation of mononuclear cells around many congested blood vessels, severe degeneration and swelling of hepatocytes throughout the parenchyma in liver; severe depletion of lymphoid cells, reticular cell hyperplasia and depletion of red pulp. In kidney severe congestion of large blood vessels and interstitial hemorrhages, vacuolation of glomeruli of the renal tubular epithelial cells and infiltration of mononuclear cells in interstitium was observed. In brain, presence of degeneration of neurons brain; congestion of the large blood vessels and in lungs thickening of interalveolar septa due to mononuclear cells infilteration were observed in cyclophosphamide treated rats which were ameliorated by treatment with CAHE in a dose dependent manner after 28 days in rats. Thus, it can be concluded from the present study that hydroethanolic extracts of C. Album has hepatoprotective and immunostimulant potential against cyclophosphamide induced toxicity.