Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na⁺-K⁺-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na⁺-K⁺-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na⁺-K⁺-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.     

联合氢气吸入的液体复苏方案对脓毒性休克大鼠肾脏的保护作用

目的:评价联合2%氢气吸入的液体复苏方案对脂多糖(LPS)诱导的脓毒性休克大鼠肾脏的治疗效果。方法:60只Wistar大鼠随机分成4组(每组15只):正常对照(control)组,脓毒性休克(shock)组,脓毒性休克+液体复苏组(fluid组),脓毒性休克+2%氢气吸入联合液体复苏组(fluid+H_2组)。大鼠麻醉后予呼吸机辅助通气,fluid+H_2组给予2%氢气空气混合气,其余3组给予单纯空气吸入。10 mg/kg LPS静脉注射,建立脓毒性休克模型,control组给予等量生理盐水静脉注射。Fluid组和fluid+H_2组给予相同液体复苏方案,维持平均动脉压于正常水平。4 h后,大鼠经腹主动脉放血处死,留取血液及肾脏标本。结果:联合2%氢气吸入的液体复苏方案与单纯液体复苏比较,血肌酐、尿素氮、中性粒细胞明胶酶相关脂质运载蛋白及肾脏组织TNF-α、IL-6水平明显降低,氧化应激损伤程度明显减轻。结论:联合2%氢气吸入的液体复苏方案更能减轻脓毒症所致急性肾损伤。     

Influence of Olmesartan on Sirtuin 1 mRNA Expression in 5/6 Nephrectomized Spontaneously Hypertensive Rats

Background

Recent studies revealed that sirtuin 1 (SIRT1) has a relation to the mechanism of transforming growth factor-beta (TGF-beta) mediated apoptosis in glomerular mesangial cells and plays an important role in blood pressure regulation. It has been suggested that SIRT1 contributes to the renoprotective effect of angiotensin receptor blocker (ARB), but this has not yet become clearly recognized. In this study, we examined the relationship between SIRT1 and the therapeutic effect of olmesartan on renal injury in nephrectomized spontaneously hypertensive rats (SHRs).

Methods

Male Wistar rats and 5/6 nephrectomized (5/6Nx) SHRs were assigned to 5 groups as follows: group A, Wistar rats; group B, Wistar rats administered high-dose olmesartan (15 mg/kg/day); group C, 5/6Nx SHRs; group D, 5/6Nx SHRs administered low-dose (3 mg/kg/day) olmesartan; and group E, 5/6Nx SHRs administered high-dose olmesartan. The drugs were administered for 12 weeks. Blood pressure and urinary protein excretion were measured every 4 weeks. Serum creatinine, glomerular sclerosis, SIRT1 mRNA level, TGF-beta mRNA level and klotho mRNA level were measured at the end of the examination.

Results

Systolic blood pressure, urinary protein excretion, serum creatinine and glomerular sclerosis in Wistar rats were significantly lower than that of 5/6Nx SHRs. Among 5/6Nx SHRs, high doses of olmesartan significantly decreased urinary protein excretion, serum creatinine and glomerular sclerosis compared to the non-treated and low-dose olmesartan groups. Expression of SIRT1 and klotho mRNA were significantly downregulated in 5/6Nx SHRs; however, olmesartan did not attribute to any change in gene expression. Expression of TGF-beta mRNA was significantly increased in 5/6Nx SHRs, and olmesartan did not affect the level of TGF-beta mRNA expression.

Conclusion

Expression of SIRT1 is decreased in 5/6Nx SHRs compared to Wistar rats. Olmesartan suppressed glomerular sclerosis, but did not increase the expression of SIRT1, suggesting that the renoprotective effect of olmesartan is independent of the SIRT1 pathway.     

苦参素降低大鼠肾脏缺血-再灌注损伤

目的观察苦参素的抗大鼠肾缺血再灌注损伤的作用并从抗氧化方面探讨其机制。方法用双肾肾蒂夹闭45 min建立IRI模型,将SD大鼠随机分为假手术组(sham);缺血再灌注组(I/R);苦参素治疗组(oxymatrine+I/R)。苦参素治疗组又分为高、中和低3个剂量组,在缺血再灌注前,连续7 d经腹腔注射。用自动生化仪测定血清肌酐(Scr)和尿素氮(BUN)水平,观察苦参素对肾缺血再灌注的保护作用及确定最优剂量;以最优剂量干预用分光分析法测定肾组织丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)水平。结果不同剂量组均能明显减轻肾脏IRI的病理形态学改变,改善肾功能。与I/R组相比,再灌注72 h后,MDA水平,血清肌酐(Scr)和尿素氮(BUN)水平明显降低(P<0.05);苦参素治疗组的CAT、T-SOD、GSH-Px活性改善明显(P<0.05)。苦参素无体外抗氧化作用。结论苦参素对大鼠肾缺血再灌注损伤具有保护作用,作用机制可能与调控机体的抗氧化系统有关。     

Psidium guajava leaf extract: effects on rat serum homeostasis and tissue morphology

This study investigated the effects of chronic daily administration of ethanolic extract of Psidium guajava leaf on rat serum homeostasis and tissue morphology over a period of 7?days. The animals were divided into two groups (Groups A & B) of five rats each. Group A received distilled water which is the vehicle for the ethanolic extract administration. Group B received 150 mg/kg rat weight of the ethanolic extract of P. guajava. The rats were sacrificed and samples prepared after 1, 3, 5 and 7 daily doses. There was significant increase in the serum urea and creatinine relative to control group (P?<?0.05). In contrast, the administration of the ethanolic extract of P. guajava produced a significant decrease in the concentration of serum Na⁺ after 5?days, which persisted until the end of experiment on day?7. There was no significant difference in the values of K⁺ when compared to control values (P?>?0.05). Results from the histopathological examinations of tissues revealed apparent loss of cellular architecture in animals treated with the ethanolic extract relative to control group. Observation of portal tract inflammation and scattered necrotic spots in the liver of ethanolic extract treated animals showed severity with progression of daily administration of the extract. Histolological observations of kidney in the treated group revealed tubular congestion and pronounced inflammation, which also increased in severity with progression of daily administration of the extract. We provide evidence that the daily administration of the ethanolic extract of P. guajava leaves altered the serum homeostasis and produced pathological changes in selected rat tissues.     

Subchronic administration of nandrolone decanoate in acetylcholinesterase activity in Wistar rats

Health sciences have recently discovered the medical uses of nandrolone decanoate (ND), an androgenic anabolic steroid (AAS), and reported its use in human and animal patients. Clinical evidences suggest that the AAS excess may affect the cholinergic system, which is responsible for several vital functions like learning, memory, and the organization of the movements. Thus, our aim is to research the subchronic effect of ND when administered in varying doses on the acetylcholinesterase (AChE) activity in these brain structures: cerebellum (CE), hippocampus, striatum (ST), and cortex of adult rats. We used 36 male Wistar rats, which were divided into six groups (n?=?6). The groups were divided into: G1—control (physiologic solution), G2—diluents control (only an oleaginous vehicle of vegetal origin—olive oil), G3—0.42?mg?kg^?1 of ND, G4—1.8?mg?kg^?1 of ND, G5—4.6?mg?kg^?1 of ND, and G6—10.0?mg?kg^?1 of ND. We applied the doses once every week during a 3-week period. The values obtained demonstrated a significant increase in the AChE activity (referring to ST and CE for the 4.6 and 10.0?mg?kg^?1 doses of ND). The ND causes increase in AChE activity, which could impair neurotransmission and cholinergic modulation.     

The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis

The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na⁺ balance, placing the kidney at the very centre of long‐term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na⁺ content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na⁺ could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na⁺ and that previously unidentified extrarenal, tissue‐specific regulatory mechanisms are operative regulating the release and storage of Na⁺ from a kidney‐independent reservoir. Moreover, immune cells from the mononuclear phagocyte system not only function as local on‐site sensors of interstitial electrolyte concentration, but also, together with lymphatics, act as systemic regulators of body fluid volume and BP. These studies have established new and unexpected targets in studies of BP control and thus the pathophysiology of hypertension: the interstitium/extracellular matrix of the skin, its inherent interstitial fluid and the lymphatic vasculature forming a vessel network in the interstitium. Aspects of the interstitium in relation to Na⁺ balance and hypertension are the focus of this review. Taken together, observations of salt storage in the skin to buffer free extracellular Na⁺ and macrophage modulation of the extracellular matrix and lymphatics suggest that electrolyte homeostasis in the body cannot be achieved by renal excretion alone, but also relies on extrarenal regulatory mechanisms.     

黑木耳粗提物在大鼠急性肾功能衰竭过程中的作用

 目的： 探讨黑木耳粗提物对大鼠腹腔注射顺铂诱发急性肾功能衰竭的作用及其可能机制。方法：将健康雄性Wistar大鼠32只随机分为对照组、模型组、黑木耳组及尿毒清组,每组8只。采用RT-PCR方法检测各组大鼠肾脏组织内皮素1（ET-1） mRNA的表达水平。同时测定血尿素氮（BUN）、肌酐（Cr）的含量及血气指标。结果：模型组与尿毒清组中ET-1 mRNA的表达,BUN和Cr的含量均高于对照组和黑木耳组（P<0.05）,而黑木耳组中ET-1 mRNA的表达与对照组比较差异无统计学意义（P>0.05）。血气分析也表明,黑木耳组发生了代偿性的酸碱平衡紊乱,且血K+浓度与对照组比较差异无统计学意义（P>0.05）。结论：黑木耳粗提物在急性肾功能衰竭过程中可能通过影响血管活性物质的合成与释放,调节体内电解质和酸碱的平衡而发挥保护作用。     

Serum biochemical assessment of hepatic and renal functions of rats during oral exposure to glyphosate with zinc

A subchronic toxicity study was carried out to assess hepatic and renal functions of rats during oral exposure to glyphosate with zinc for the period of 8 weeks. Forty-eight Wistar rats used for the study were randomized into six groups of eight Wistar rats each, and each group had equal number of male and female Wistar rats. The Wistar rats administered with distilled water at 2 ml/kg body weight served as the control group (DW); others were administered with zinc at 50 mg/kg body weight (Z) group, glyphosate at 375 mg/kg body weight (G) group, a combination of zinc and glyphosate at 50 and 375 mg/kg body weight, respectively (Z?+?G), group, glyphosate at 14.4 mg/kg body weight (GC) group, and a combination of zinc and glyphosate at 50 and 14.4 mg/kg body weight, respectively (Z?+?GC), group. At the end of the study, blood samples were collected from each rats; from which, sera samples were obtained and assayed for total protein, albumin, alanine and aspartate aminotransferases, alkaline phosphatase, Na⁺, K⁺, Cl^?, \( \mathrm{HCO}_3^{-} \) , Ca²⁺, \( \mathrm{PO}_4^{-} \) , urea and creatinine using autoanalyzer, and globulin was calculated. The albumin concentration was significantly high (p?<?0.05) in GC group compared to DW group, and this change was ameliorated following supplementation with zinc. The total protein and globulin concentrations did not differ significantly between the groups (p?>?0.05), and the relative changes were ameliorated by supplementation with zinc. The alkaline phosphatase activity was relatively low in GC group; however, supplementation with zinc in Z?+?GC group made it to be significantly high (p?<?0.05) compared to GC group. The alanine and aspartate aminotransferases in G and GC groups were relatively high compared to DW group, which were ameliorated by supplementation with zinc. The relatively low Ca²⁺ concentration in G and GC groups compared to DW were ameliorated in Z?+?G group, and it was significantly high in Z?+?GC group at p?<?0.01 compared to DW, p?<?0.001 compared to G and GC groups and p?<?0.05 compared to Z?+?G group. There were only slight changes in the electrolytes concentrations (Na⁺, K⁺, Cl^?, \( \mathrm{HCO}_3^{-} \) and \( \mathrm{PO}_4^{-} \) ), which were differentially ameliorated by zinc supplementation. The reasons for the various changes recorded were discussed. It was concluded that subchronic oral exposure to glyphosate caused both hepatic and renal functions toxicity in rats, which were ameliorated by zinc supplementation.     

Safety evaluation of <Emphasis Type="Italic">Acalypha wilkesiana</Emphasis> in albino rats and BHK-21 cell line

Acalypha wilkesiana is a member of the spurge family, genus Acalypha, that is widely used in folklore medicine. The aim of this study was to screen aqueous leaf extract of A. wilkesiana for toxic effects in vitro and in vivo. We examined the phytochemical profile, cytotoxic effects on baby hamster kidney cell line (BHK-21), and oral subacute toxicity of A. wilkesiana leaf decoction in rats. Rats were given 0, 300, 600, and 1200 mg/kg body weight of A. wilkesiana leaf extract, daily, orally for 14 days. The phytochemical profile showed the presence of flavonoids, saponin, cardiac glycosides, and tannins. It caused apoptosis in BHK-21 cell line at concentrations of 0, 25, 50, 100, and 200 μg/ml. There was significant increase in the levels of serum AST, ALT, creatinine, urea, Na⁺, K⁺, and Cl^? levels in all the test groups compared to the control. Histology of the liver revealed centrilobular degeneration and necrosis with sinusoidal dilatation as well as polymorphonuclear and mononuclear infiltration. The kidney showed severe glomerular and tubular degeneration and necrosis with hemorrhage at all doses administered. We conclude that the plant was toxic at the doses tested in vitro and in vivo, and care should be exercised in its use in herbal medicine.     

Renal handling of salt and water in humans during exercise with or without hydration

Plasma sodium (Na⁺) concentration, i.e. natraemia, results from body tonicity equilibrium. During exercise, a change in body tonicity can result from an imbalance between intake and loss of Na⁺, potassium (K⁺) and water (H₂O) due to renal and/or extra-renal mechanisms. Whether exercise-induced changes in kidney function could be responsible for such an imbalance was studied by measuring glomerular filtration rate (creatinine clearance), proximal tubule activity (lithium clearance) and renal handling of Na⁺ and K⁺ at rest and during exercise. Since hyponatraemia during or after exercise has been reported, we also investigated whether a water load could be appropriately excreted during exercise. Ten young men pedalled on a cycle ergometer at 60% of maximal oxygen uptake for 45 min with (HE, hydrated exercise) or without (DHE, dehydrated exercise) a supply of water. In both conditions, creatinine, lithium, and electrolyte (Na⁺+K⁺) clearances decreased and natraemia did not change. The DHE induced a loss of body mass (–1.29%), decreased diuresis and large extra-renal water loss [mean (SEM)] [880 (73) ml]. The HE led to no loss in body mass, increased diuresis and lower extrarenal water loss [680 (48) ml]. Electrolyte-free water excretion, negative for DHE, represented 60% of diuresis during HE. Thus the kidney, by increasing electrolyte reabsorption mainly in the proximal tubule, and appropriately excreting a water load, seems efficacious in regulating extracellular fluid volume and body tonicity and so not responsible for the imbalance between (Na⁺+K⁺)/H₂O intake and loss. Therefore, extra-renal changes could be the main causes of exercise-induced tonicity imbalances which could ultimately lead to dysnatraemia. Electronic Publication     

Erythropoietin response to acute hypobaric or anaemic hypoxia in gentamicin-administered rats

In an attempt to assess the erythropoietin (Epo) production site(s) in rat kidney, Epo response to hypoxia and renal histopathological changes were studied in rats administered with graded doses of gentamicin. Male Sprague-Dawley rats of 9 to 11 weeks old were used. Following a 14-day subcutaneous administration (67.5 or 33.8 mg kg^-1 day^-1) of gentamicin, a nephrotoxic aminoglycoside, selective proximal tubular lesions were produced. These gentamicin-administered rats were compared with normal rats with respect to Epo response to hypoxia. Two different kinds of hypoxic load, either 0.35 atm hypobaric hypoxia (P_IO2= 46 torr) or acute anaemia (Ht: 29.3 ± 0.2% and [Hb]: 9.7 ± 0.3 g dl^-1) by withdrawing of blood corresponding to 1–2% of body weight was used. During the hypoxic period of up to 48 h, the peak renal venous plasma Epo titres of 3.1 ± 0.6 and 4.3 ± 0.6 U ml^-1 was observed at the 6th h in normal hypobaric hypoxic and anaemic rats, compared with the prehypoxic value of 0.7 ± 0.1 U ml^-1. The Epo titres then declined gradually. In the rats which were administered gentamicin, Epo response pattern was the same as that observed in the normal rats, but the peak value decreased significantly to 0.8 ± 0.3 and 1.1 ± 0.4 U ml^-1 in hypoxic and anaemic rats (P < 0.05). Histological examination revealed the selective damage to renal proximal convoluted tubules. The Epo response was reduced by the tissue damages, and restoration of the gentamicin-induced tissue injury was accompanied with restored Epo response to hypoxia. The results suggest that renal proximal convoluted tubules are involved in Epo production under hypoxia.     

肾缺血再灌注模型细胞凋亡与吡咯烷二硫代氨基甲酸的干预

背景：肾缺血/再灌注诱导产生大量活性氧,导致核因子κB的活化。激活的核因子κB通过调节诱导型一氧化氮合酶的生成,进而导致一氧化氮的大量产生和触发细胞凋亡。 目的：观察吡咯烷二硫代氨基甲酸对肾缺血再灌注后肾脏组织中核因子κB、诱导型一氧化氮合酶、一氧化氮、caspase-3和细胞凋亡指数的作用。 方法：将健康雄性Wistar大鼠随机分为3组：缺血再灌注组和吡咯烷二硫代氨基甲酸组通过右侧肾切除+左肾动脉夹闭 45 min建立肾缺血/再灌注模型,吡咯烷二硫代氨基甲酸组于实验前30 min尾静脉注射吡咯烷二硫代氨基甲酸 (100 mg/kg)。假手术组不给予缺血再灌注处理。 结果与结论：与假手术组相比,缺血再灌注组大鼠再灌注后肾组织核因子κB表达水平、血肌酐水平、尿素氮水平、诱导型一氧化氮合酶活性、一氧化氮表达水平、caspase-3表达水平和细胞凋亡水平增加(P < 0.05);而与缺血再灌注组相比,吡咯烷二硫代氨基甲酸组大鼠再灌注后以上指标均好转。说明肾缺血/再灌注损伤可引起肾组织结构损伤和细胞凋亡,且与核因子κB引起的一氧化氮高表达有关;应用核因子κB抑制剂吡咯烷二硫代氨基甲酸可对缺血再灌注肾损伤发挥明显的保护作用。     

Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes

Myricetin is a naturally occurring flavonoid that is known to decrease plasma glucose levels in diabetes; however, its influence on renal functions has not yet been determined. This study investigated the effect of myricetin on structural and functional changes occurring in diabetic nephropathy. Male Albino Wistar rats were divided into three groups: normoglycemic, diabetic and myricetin-treated diabetic. Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50?mg/kg), and rats having fasting blood glucose (FBG) levels greater than 200?mg/dl were included in the study. Treatment of myricetin (6?mg/day ip) was initiated 16?weeks after diabetes was confirmed. Light microscopy was performed on hematoxylin-eosin- and Masson's trichrome-stained sections to evaluate the effect of myricetin on structural changes in the kidney, while creatinine clearance, blood urea nitrogen (BUN), kidney weight, urine volume and protein were measured to assess kidney functions. Activities of glutathione peroxidase (GPx) and xanthine oxidase (XO) were also measured in renal tissues obtained from all experimental groups. Myricetin treatment significantly decreased glomerulosclerosis and reduced BUN, urinary volume and protein excretion, which was profoundly increased in diabetic rats. Decreased creatinine clearance measured in diabetic rats was significantly increased following myricetin treatment. Myricetin also restored altered renal activities of GPx and XO, which were decreased and increased in diabetic rats, respectively. In conclusion, myricetin improved altered renal functions and restored renal activities of GPx and XO in diabetic rats. Obtained data suggest that myricetin could be of therapeutic potential in diabetic nephropathy.     

Catechin,quercetin and taxifolin improve redox and biochemical imbalances in rotenone-induced hepatocellular dysfunction: Relevance for therapy in pesticide-induced liver toxicity?

Hepatotoxicity occurs as a result of adverse effects of some xenobiotics on the liver, which is often the target tissue of toxicity for environmental chemicals. Rotenone, used as a natural pesticide, is an environmental poison reported to cause organ toxicity. This study investigated the protective effect of three flavonoids, catechin, quercetin and taxifolin (2,3-Dihydroquercetin) in rotenone-induced hepatotoxicity. Male Wistar rats were administered rotenone for 10 days followed by post treatment with catechin (5, 10 and 20?mg/kg), quercetin (5, 10 and 20?mg/kg) or taxifolin (0.25, 0.5 and 1?mg/kg), respectively, for 3 days. Bioindices of oxidative stress and hepatocellular injury were measured in serum and tissue homogenate of animals. Rotenone intoxication produced liver damage in rats as reflected in alterations to activities/levels of enzymic and non-enzymic oxidative stress markers and enzymes linked with inflammation, as well as the transaminases, gamma glutamyl transpeptidase, bilirubin, and lactate dehydrogenase. Catechin, quercetin and taxifolin post treatment significantly attenuated these (p?<?0.0001) rotenone-induced imbalances. Comparatively, quercetin displayed the best apparent ameliorative activity. It clearly showed superior activity to catechin. However, taxifolin appeared to show comparable activity to quercetin and better activity than catechin in some of the assays despite being administered at considerably lower doses. The results provide insight on the relative efficacy and structure-activity relationships of the selected flavonoids in ameliorating liver damage and also indicate that additional structural and metabolic factors may be involved in the structure-activity relationships of flavonoids.     

Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury

The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10)?g] were either assigned as non-exercised controls or subjected to 30?min of treadmill exercise (grade, ?16°; speed, 15?m?·?min^?1), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n?=?5–6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd⁺) were seldom detected in the TA. In the VI and S, higher proportions of MHCd⁺ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P?≤?0.01). In S, MHCd⁺ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd⁺ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd⁺ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd⁺ fibres were smaller (<2500?μm²) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd⁺ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.     

Cyclosporine A disposition,hepatic and renal tolerance in Wistar rat

Cyclosporine A, a potent calcineurin inhibitor, has been widely used in organ transplantation and in the treatment of autoimmune diseases. It has, however, been shown to induce serious renal and hepatic side effects. The drug is also used in preclinical studies, but with little published information on the optimal dose and route of administration in rodents. Objectives of this study were to identify efficient and safe doses of cyclosporine A in rodent and to assess its effects on hepatic and renal functions. For this purpose, we tested the effects of different doses and administration routes of cyclosporine A (5, 2.5 and 1?mg/kg) administered during 28 days intraperitoneally, or by gastric feeding on Wistar rats. Our data indicate that rats injected intraperitoneally with 5?mg/kg/2d (every two days) exhibited trough cyclosporine A levels within known therapeutic range in human, but were subject to blood cyclosporine A accumulation, whereas the 5?mg/kg/d gavage resulted in only a small cyclosporine A accumulation over time. In both cases this accumulation was not deleterious to renal and hepatic functions, as shown by transaminase, urea, creatinine and bilirubin measurements.     

Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats

Background

Nanoparticles are small-scale substances (<100?nm) with unique properties. Therefore, nanoparticles pose complex health risk implications. The objective of this study was to detect whether treatment with quercetin (Qur) and/or arginine (Arg) ameliorated nephrotoxicity induced by two different doses of nano zinc oxide (n-ZnO) particles.

Method

ZnO nanoparticles were administered orally in two doses (either 600?mg or 1?g/Kg body weight/day for 5 conscutive days) to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed.

Results

Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-??), interleukin-6 (IL-6); and C-reactive protein (CRP). Moreover, immunoglobulin (IGg), vascular endothelium growth factor (VEGF), and nitric oxide (NO) were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH) was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters.

Conclusions

The data show that Qur has a beneficial effect against n-ZnO oxidative stress and related vascular complications. Also, its combination with Arg proved to be even more effective in ameliorating nano zinc oxide nephrotoxicity.     

The effects of bisphenol A on some plasma cytokine levels and distribution of CD8+ and CD4+ T lymphocytes in spleen,ileal Peyer’s patch and bronchus associated lymphoid tissue in rats

The effects of bisphenol A on the some plasma cytokine levels and distribution of CD8⁺ and CD4⁺ T lymphocytes in spleen, ilealPeyer’s patch and bronchus-associated lymphoid tissue in rats were investigated. A total of fourty male Wistar Albino rats were divided into five groups including 8 rats in each one: control, vehicle, BPA 5, BPA 50 and BPA 500 groups. Doses of 5, 50 and 500?μg/kg BPA were dissolved in ethanol, then mixed with corn oil. The control group received no treatment. The vehicle group was given the ethanol-corn oil mixture. BPA 5, BPA 50 and BPA 500 groups were given, respectively, 5, 50, and 500?μg/kg/day orally. In blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA. Tissue samples (spleen, ileal Peyer’s patches and lung) were processed by means of routine histological techniques. CD4 and CD8 were stained immunohistochemically. Data obtained from this study showed that, BPA causes the alteration on immune parameters including cytokine profile, distribution of CD8⁺ and CD4⁺ T lymhpocytes in spleen and ileal Peyer’s patches. Present study indicated that BPA may affect immune systems even at lower doses.Disruption of immun system cells and cytokine levels can result in harmful outcomes triggering autoimmune diseases and immunodeficiencies.     

Comparison of adverse drug reaction profiles of two tacrolimus formulations in rats

Tacrobell^® (TB) is a generic tacrolimus which showed the comparable efficacy to original product, Prograf^® (PG) in renal transplantation, but toxicity between two drugs is unclear. The aim of this study was to compare the toxicity between these two formulations. TB and PG (0.5, 1 and 2?mg/kg/day) was administered to rats for 4 weeks. The rat survival rate, kidney, liver and pancreas injury was investigated. The survival rate was similar between TB- and PG-treated rats. TB and PG induced renal dysfunction in a dose-dependent manner. Compared to PG treatment in equal dose, TB treatment reduced urinary creatinine clearance in a less degree and renal interstitial fibrosis was comparable between two regimens. The r-glutamyl transpeptidase was aggravated by tacrolimus treatment, and this was not different between TB and PG treatment. In the intraperitoneal glucose tolerance test, a significant diabetogenic effect was observed in all tacrolimus treated-rats. The glucose tolerance of TB-treated rats was similar to those of PG-treated rats in each dose. The decrement in pancreatic β-cell mass by tacrolimus showed the dose-dependent response and it was comparable between TB and PG treatment. In conclusion, TB is similar to PG in terms of nephrotoxicity, hepatoxicity and diabetogenic effect.