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The bioavailability and pharmacokinetic disposition of tiamulin in broiler chicken were investigated after administration through the crop, drinking water, and feed at 40 mg/kg body weight. Residues of tiamulin in tissues of broiler chicken were also assessed. Plasma and tissue concentrations of tiamulin were analyzed by reverse-phase high-performance liquid chromatography (HPLC) method. Plasma concentration-time data were described by the non-compartmental model for all three routes, and pharmacokinetic parameters were calculated. There were no significant differences (p > 0.05) in pharmacokinetic parameters and mean plasma concentrations of tiamulin between three routes tested (crop, water, and feed), indicating equal efficacy. Tiamulin residues in edible tissues (muscles, skin, and fat) were lower than the advocated maximum residue limit (MRL of 0.1 µg/g and that of liver was 1 µg/g) on the 3rd day. No traces were found on the 5th day after drug administration. This indicated that the withdrawal period (less than 5 days) is very short, which makes it safer. This study shows that tiamulin can be used with equal efficacy through all routes of administration in broiler chicken (crop, water, and feed)., (© 2019 John Wiley & Sons Ltd.)

We report the detailed gross, histopathological and immunohistochemical study of Strobilocercus fasciolaris infection, the metacestodal stage of Taenia taeniaeformis, in the liver of laboratory Wistar rats. Necropsy examination of seventeen rats revealed transparent or white or cream to clear, thick walled cysts, 1 to 97 in number, measuring about 2mm to 12mm on one or many of the liver lobes and containing strobilocercus of Taenia taeniaeformis. Histopathological examination revealed the presence of the cross-section of larva surrounded by a thick fibrous capsule and moderate infiltration of lymphocytes, plasma cells and a few eosinophils. Fatty degeneration of hepatocytes, gastric mucosal hyperplasia, distended gastric glands and marked increase in the mucosal epithelial cells and goblet cells in the duodenum were also observed. Contamination of feed and bedding materials seems to be the probable source in these naturally infected rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Seaweeds or marine algae have long been made up a key part of the Asian diet, and as an antioxidant, sulphated polysaccharides have piqued the interest of many researchers as one of the ocean's greatest treasures. The present investigation suggests the therapeutic potential of sulphated polysaccharides from marine brown algae "Sargassum wightii" in Cyclosporine A (CsA)- induced liver injury. CsA is a potent immunosuppressive agent used in the field of organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains to be one of the major clinical challenges., Methods: The effect of sulphated polysaccharides on CsA-induced hepatotoxicity was studied in adult male albino rats of Wistar strain, and the animals were randomized into four groups with six rats in each. Group I served as vehicle control. Group II rats were given CsA at a dosage of 25 mg/kg body weight, orally for 21 days. Group III rats were given sulphated polysaccharides at a dosage of 5 mg/kg body weight, subcutaneously for 21 days. Group IV rats were given sulphated polysaccharides simultaneously along with CsA, as mentioned in Group II for 21 days., Results: CsA provoked hepatotoxicity was evident from the decreased activities of hepatic marker enzymes. A significant rise in the level of oxidants, along with a striking decline in both the enzymic and non-enzymic antioxidants, marks the severity of oxidative stress in CsA-induced rats. This in turn led to enhanced levels of lipid peroxidation, 8-hydroxy-2-deoxy guanosine and protein carbonyls, along with a decrease in ATPase activities and alterations in lipid profile. Histopathological changes also strongly support the above aberrations. However, concomitant treatment with sulphated polysaccharides restored the above deformities to near control and prevented the morphological alterations significantly., Conclusion: Thus, the present study highlights that sulphated polysaccharides can act therapeutically against CsA-induced hepatotoxicity.

Oxalate/calcium oxalate toxicity is mediated through generation of reactive oxygen species in a process that partly depends upon events that induce mitochondrial damage. Mitochondrial dysfunction is an important event favoring stone formation. The objective of the present study was to investigate whether mitochondria is a target for oxalate/calcium oxalate and the plausible role of naturally occurring glycosaminoglycans from edible seaweed, fucoidan in ameliorating mitochondrial damage. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I: vehicle treated control, Group II: hyperoxaluria was induced with 0.75% ethylene glycol in drinking water for 28 days, Group III: fucoidan from F. vesiculosus (5 mg/kg b.wt, s.c) from the 8th day of the experimental period, Group IV: ethylene glycol+fucoidan treated rats. The tricarboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and respiratory complex enzyme activities were assessed to evaluate mitochondrial function. Oxidative stress was assessed based on the activities of antioxidant enzymes, level of reactive oxygen species, lipid peroxidation and reduced glutathione. Mitochondrial swelling was also analyzed. Ultra structural changes in renal tissue were analyzed with electron microscope. Hyperoxaluria induced a decrease in the activities of TCA cycle enzymes and respiratory complex enzymes. The oxidative stress was evident by the decrease in antioxidant enzymes, glutathione and an increase in reactive species and lipid peroxidation in mitochondria. Mitochondrial damage was evident by increased mitochondrial swelling. Administration of fucoidan, decreased reactive oxygen species, lipid peroxidation (P<0.05), mitochondrial swelling and increased the activities of antioxidant enzymes and glutathione levels (P<0.05) and normalized the activities of mitochondrial TCA cycle and respiratory complex enzymes (P<0.05). From the present study, it can be concluded that mitochondrial damage is an essential event in hyperoxaluria, and fucoidan was able to effectively prevent it and thereby the renal damage in hyperoxaluria.

Sulfated polysaccharides from marine seaweeds are receiving continuous attention owing to their wide therapeutic applications and are known to inhibit free radical generation. It has been well known that mitochondria are the major sources as well as the target of free radicals. The renal tubules have high density of mitochondria and therefore show structural and functional defects in acute renal failure. Hence, the present study is designed to appraise the mitochondrial status during Cyclosporine A (CsA)-induced nephrotoxicity and the effect of sulfated polysaccharides over it. Sulfated polysaccharides (5 mg/kg body weight, subcutaneously) treatment significantly prevented the CsA-induced (25 mg/kg body weight, orally) mitochondrial damage. CsA-induced mitochondrial oxidative stress in rat kidney was evident from increased reactive oxygen species level, decreased antioxidant defense system, coupled with enhanced lipid peroxidation. Further, the activities of tricarboxylic acid cycle and electron transport chain enzymes were decreased in CsA-induced rats, along with a significant increase in the activities of urinary enzymes, thus indicating renal tubular injury. Ultrastructural changes were also in accord with the above aberrations. The above abnormalities were favorably modulated by sulfated polysaccharides supplementation, thus highlighting the significance of sulfated polysaccharides in preventing the renal mitochondrial dysfunction allied with CsA-provoked nephrotoxicity.

The scope of the current study was to examine the possible effects of sulphated polysaccharides against cyclosporine A-induced glomerular injury. Nephrotoxicity induced by cyclosporine A continues to be a major problem despite its potent immunosuppressive action. Adult male albino rats of Wistar strain were categorized into four groups. Two groups (II and IV) were administered cyclosporine A (25 mg/kg body weight, orally) for 21 days, in which Group IV rats were also treated simultaneously with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) for the same period. A significant loss in body weight was noted in the cyclosporine A-induced rats. Renal damage was assessed in terms of decreased creatinine clearance and increased activity of lysosomal enzymes. The levels of glycoproteins were found to be decreased in the renal tissue, and a noticeable rise in glycosaminoglycanuria coupled with marked proteinuria was more prominent in the cyclosporine A-induced animals. Furthermore, the extent of kidney damage was assessed by histopathological findings. Toxic manifestations were also confirmed by transmission electron microscopic studies. These morphological abnormalities and other alterations in the renal tissue were significantly offset by sulphated polysaccharides supplementation. These findings underline that restoration of normal cells accredits sulphated polysaccharides, from Sargassum wightii, with nephroprotective role, against cyclosporine A-induced renal injury.

Oxidative and nitrosative stress are known to exert various adverse effects on biological systems and this seems to be one of the major contributor of nephrotoxicity induced by cyclosporine A (CsA), which is a major clinical challenge, despite its potent immunosuppressive effect. Sulphated polysaccharides of marine origin are well known for its antioxidant properties, among its other biological applications. CsA administration (25 mg/kg body weight, orally, for 21 d) showed increased level of oxidants and xanthine oxidase activity. CsA induced nitrosative stress was evident from a marked elevation in the expression of inducible nitric oxide synthase mRNA in renal tissue and a concomitant increase in plasma nitric oxide level. Augmented levels of malondialdehyde, 8-hydroxy-2-deoxyguanosine and protein carbonyl coupled with diminished protein thiols; hallmarks of lipid peroxidation, DNA damage and protein oxidation were noted in CsA administered rats. Membrane damage was further confirmed by altered ATPase activities in the renal tissue. Simultaneous treatment with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) remarkably prevented the above alterations mediated by oxidative and/or nitrosative stress during CsA induction. Hence, these findings conclude that the use of an antioxidant agent like sulphated polysaccharides could be a useful tool in reducing CsA-induced nephrotoxicity.

Cyclosporine A (CsA)-induced nephrotoxicity hampers the immense therapeutic potential of such a powerful immunosuppressant. The present study was conducted with an aim to explicate the contribution of sulphated polysaccharides (SPS) in abating the lipid abnormalities induced by CsA in the rat kidney. Hyperlipidemia associated with nephrotic syndrome may play a role in the worsening of renal function. Male albino Wistar rats sorted into four groups were used for the study. CsA was given at a dose of 25 mg/kg body weight, orally for 21 days. Significant alterations in the lipid profile as well an increase in the activity of cholesterol ester synthase, coupled with a decrease in cholesterol ester hydrolase and lipoprotein lipase enzyme activities were noted in the plasma and kidneys of CsA-administered rats. A marked increase in the lipoprotein fractions, low-density lipoprotein (LDL) and very low density lipoprotein (VLDL), along with a decrease in the HDL level were found in CsA-administered rats. The degree of nephrotoxicity allied with lipid discrepancies was evident from augmented urinary excretion of urea, uric acid and creatinine. Further, an enhanced susceptibility of the apo B-containing lipoproteins (LDL + VLDL) to oxidation in vitro, induced by copper ions was also found in the plasma of CsA given groups. While SPS co-treated groups (5 mg/kg body weight, subcutaneously) revealed a normalized lipid profile and lipid metabolizing enzymes, the supplementation of SPS also brought back the elevated urinary constituents close to that of the controls and substantially minimized the oxidative changes. With these observations, it may be concluded herein that SPS may be an ideal choice as a renoprotective and hypolipidemic agent against CsA-induced hyperlipidemic nephropathy.

Urinary supersaturation-induced crystal formation has been attributed as one of the key factor for the pathogenesis/progression of lithogenesis. This study was aimed at investigating whether fucoidan, a naturally occurring sulfated glycosaminoglycan, could ameliorate the biochemical changes in urine induced by stone formation. Two groups of male albino Wistar rats (120+/-20 g) received 0.75% ethylene glycol (EG) for 28 days to induce hyperoxaluria, and one of them received sulfated polysaccharides (fucoidan from Fucus vesiculosus, 5 mg kg(-1), s.c.), commencing from the 8(th) day of the experimental period. One group was maintained as normal control group and another group served as drug control, which received sulfated polysaccharides. The urine collected from all the groups was analysed for changes in pH, volume, oxalate, calcium, phosphorus, uric acid, magnesium, citric acid and glycosaminoglycans. Urinary crystals were analysed with a light microscope. Renal tissues were studied under polarized light for deposition of crystals and also analysed for their oxalate and calcium content. The changes in extracellular matrix on crystal deposition were also evaluated. The urinary pH and volume were altered in rats treated with EG along with an increase in weight of the kidney. Further, administration of EG to rats increased the supersaturation of urine by escalating the levels of the stone-forming constituents, such as oxalate, calcium, phosphorus and uric acid, which was completely restored by fucoidan treatment. The decrease in the inhibitors, like citrate, magnesium and glycosaminoglycans, in urine was prevented by the co-treatment with fucoidan. In hyperoxaluric rats, there was an increased excretion of calcium oxalate monohydrate crystals in urine along with crystal deposition in renal tissues; this was prevented by fucoidan treatment. Fucoidan administration reversed even the tissue levels of calcium and oxalate. The increased accumulation of collagen and expression of transforming growth factor-beta(1) in hyperoxaluria was normalized on fucoidan administration. These results suggest that the physico-chemical alterations in urine produced during hyperoxaluria can be reversed by fucoidan administration.

Oxalate, one of the major constituents of renal stones is known to induce free radicals which damage the renal membrane. Damaged epithelia might act as nidi for stone formation aggravating calcium oxalate precipitation during hyperoxaluria. In the present study, the beneficial effects of fucoidan on oxalate-induced free radical injury were investigated. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two groups by administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with fucoidan from Fucus vesiculosus at a dose of 5 mg/kg b.wt subcutaneously commencing from the 8th day of induction. A control and drug control (fucoidan alone) was also included in the study. The extent of renal injury in hyperoxaluria was evident from the increased activities of alkaline phosphatase, gamma-glutamyl transferase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase in urine. There was a positive correlation between plasma malondialdehyde levels and renal membrane damage indicating a striking relation between free radical formation and cellular injury. Increased protein carbonyl and decreased thiols further exemplified the oxidative milieu prevailing during hyperoxaluria. Decreased renal membrane ATPases accentuated the renal membrane damage induced by oxalate. Renal microscopic analysis showed abnormal findings in histology as an evidence of oxalate damage. The above biochemical and histopathological discrepancies were abrogated with fucoidan administration, indicating its protective role in oxalate mediated peroxidative injury.

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.

Cyclosporine A (CsA) has been universally used as an immunosuppressant for the management of organ transplantation and various autoimmune diseases. However, nephrotoxicity due to CsA remains to be an important clinical challenge. In the present investigation, an attempt has been made to appraise the effect of sulphated polysaccharides on oxidative renal injury caused by CsA. Adult male Wistar rats were divided into four groups. Two groups received CsA by oral gavage (25 mg/kg body weight) for 21 days to provoke nephrotoxicity, one of which simultaneously received sulphated polysaccharides subcutaneously, (5 mg/kg body weight). A vehicle (olive oil) treated control group and sulphated polysaccharides drug control were also built-in. An increase in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamin C and vitamin E) are the salient features observed in CsA induced nephrotoxicity. CsA induced impairment of renal toxicity was evident from the marked decline in the activities of renal marker enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase, as well as an apparent increase in the serum urea, uric acid and creatinine; diagnostic of renal damage was normalized by sulphated polysaccharides co-administration. Sulphated polysaccharides treatment showed an effectual role in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. These observations emphasize the antioxidant property of sulphated polysaccharides and its cytoprotective action against CsA induced nephrotoxicity.