Therapeutic effect of cimetidine on acetaminophen-induced nephrotoxicity in rats

Acetaminophen as an analgesic and antipyretic drug can induce renal toxicity in high doses. Cimetidine as an H₂-blocker can inhibit the cytochrome P450 enzymes and reduce the toxic effect of acetaminophen on renal tissue. Eighty rats in eight groups comprising normal control group, acetaminophen control group, cimetidine control group, and five different treatment groups (cimetidine was administrated at 0, 1, 2, 4, and 8 h after acetaminophen administration) were used. Acetaminophen was administered at a toxic of dose 3 g/kg orally, and cimetidine (12.5 mg/kg) was administrated by intraperitoneal route at different times after induction of toxicity. Creatinine and urea were measured, and pathologic lesions were determined. In treatment groups 3 and 6, the urea and creatinine concentration showed no significant difference from group 1. In other treatment groups, the urea and creatinine concentrations were increased significantly (p < 0.05). Histopathologic changes in group 6 were mild in comparison to other groups. We concluded that administration of cimetidine at least 2 h after acetaminophen toxicity can reduce renal lesions.     

Therapeutic effect of cimetidine on acetaminophen-induced hepatotoxicity in rabbits

Acetaminophen is an analgesic and antipyretic drug that may cause hepatic toxicity in humans and experimental animals. Cimetidine is an H₂ blocker used for suppression of gastric acid secretion. One of the side effects of cimetidine is blockade of the cytochrome P-450 enzyme system which results in increased half-life of some drug. In this study, 120 female rabbits, randomized into 12 groups (three control and nine test groups), were used. Acetaminophen, 3.24 g/kg, in suspension form as the LD₅₀, was administered orally to induce liver necrosis. Cimetidine (40 mg/kg) was administered intravenously at 0, 2, and 4 h after administration of acetaminophen. Some treatment groups received cimetidine in two equal divided doses—20 mg/kg cimetidine was administered at 2 and 12 h, 2 and 24 h, 4 and 12 h, and 4 and 24 h after administration of acetaminophen. Blood samples were collected at 0, 12, 24, and 36 h after induction of acetaminophen toxicity. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and arginase were measured in all groups and were found to be increased in acetaminophen control group and some treatment groups (p < 0.05). Results showed that the best treatment effect of cimetidine could be obtained with whole dose of cimetidine administration and 2 h after acetaminophen intake.     

Therapeutic effects of cimetidine on acetaminophen-induced hepatotoxicity in rats

Acetaminophen is a widely used analgesic and antipyretic drug. An overdose can cause life-threatening hepatotoxicity in humans and experimental animals. In this study, 80 female Sprague–Dawley rats randomized into eight groups (three control and five test groups) were used. Three milligrams per kilogram acetaminophen was administered orally to induce liver necrosis. Cimetidine (12.5 mg/kg) was administered intraperitoneally at 0, 1, 2, 4, and 8 h after acetaminophen administration. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and extent of pathologic changes in liver were evaluated in all groups (1–8), and were found to be increased in group 2 (acetaminophen control), but not in groups 1 and 3 (control groups), and were decreased in some treatment groups. The decrease observed in groups 7 and 8 was more than that in group 6. However, in these groups, more animals died due to toxicity before blood sampling. It was concluded that injection of cimetidine 2 h after acetaminophen administration (group 6) can markedly decrease the serum levels of ALT, AST, and the extent of pathologic lesions in the liver with minimal toxicity and death.     

Effect of cimetidine on experimental atherogenesis in rabbits

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, N ^o 4, pp. 380–383, April, 1993     

Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation.     

川芎嗪注射液对家兔失血性休克的作用

为了检查川芎嗪注射液对失血性休克的作用,失血性休克家免于输回血后分别静脉输入不同剂量的川芎嗪注射液。结果表明,休克状态下和对照组相较,输入0.1ml/kg的川芎嗪注射液可改善外周血流但不降低血压,减少血管内液外移;输入0.2ml/kg的川芎嗪注射液虽使外周血流有所改善,但使血压降低。     

Antiprostatic effect of cimetidine in rats

Administration of large doses of cimetidine for 45 days to rats decreases the weight of the prostate and seminal vesicles without affecting the testicles. The decrease in weight is due to a marked regression in the prostate of both epithelial and stromal tissue.Treatment with cimetidine also causes an increase in the plasma testosterone level without modifying the plasma values of LH and prolactin. The mechanism of action of cimetidine is discussed. In presence of high levels of testosterone, cimetidine depresses structures such as the prostate and seminal vesicles, which are sensitive to androgens, but does not depress the weight or change the histology profile of the testicles, which are also rich in androgen receptors. Perhaps cimetidine binds to androgen receptors differently in the prostate and in the testicles because of differences in receptor structure or more probably, cimetidine interacts with zinc metal ion essential to prostate growth and androgen action by lowering zinc prostatic levels and consequently depresses the prostatic weight.     

The effect of cimetidine on plasma lipoproteins

The concentration of lipids, lipoproteins and apolipoproteins A-I and -B were measured in the plasma of 12 patients with peptic ulcer disease before and after five weeks of treatment with cimetidine. No statistically significant changes were found, but HDL cholesterol and HDL2 cholesterol tended to increase, and VLDL cholesterol and plasma triglycerides tended to decrease. A review of published studies indicates that the data at present are too uncertain to warrant use of cimetidine as a lipoprotein modulating drug.     

西咪替丁对小鼠中孕妊娠影响的实验研究

目的 :初步研究西咪替丁对中孕妊娠的影响。方法 :用昆明种小鼠 ,在妊娠第 9～ 1 2天分别连续灌胃给予西咪替丁 80mg·kg 1,1 60mg·kg 1,3 2 0mg·kg 1,640mg·kg 1,于妊娠第 1 6天解剖记录活胎数 ,吸收胎死胎数。结果 :西咪替丁 1 60mg·kg 1,3 2 0mg·kg 1,640mg·kg 1剂量对小鼠的妊娠抑制率分别为 1 0 % ,45 % ( p <0 .0 0 5 ) ,65 % ( p <0 .0 0 5 )。 结论 :西咪替丁具有一定的终止中孕妊娠作用。     

西咪替丁对小儿轮状病毒肠炎的临床疗效分析

目的 探讨西咪替丁对小儿轮状病毒肠炎的临床疗效分析.方法 选择2012年1月-2015年12月收治的150例轮状病毒感染的肠炎患儿,根据随机数字表法,将所有患儿分为观察组与对照组.两组均给予常规治疗,对照组在常规治疗基础上给予利巴韦林用药,观察组在常规治疗基础上给予西咪替丁用药,观察两组患儿平均退热时间、平均止泻时间、平均止吐时间、疗效及不良反应.观察两组治疗前后的IL-2、IL-6及TNF-α水平.结果 观察组的平均退热时间、平均止泻时间、平均止吐时间明显低于对照组,观察组的总有效率明显高于对照组,治疗后两组患儿的IL-6、TNF-α均显著降低,组内对比差异明显,组间对比发现观察组明显低于对照组(P＜0.05);治疗后两组的IL-2均明显升高,组内对比差异明显,组间对比观察组明显高于对照组(P＜0.05).观察组的不良反应率低于对照组,但组间对比无统计学差异(P＞0.05).结论 西咪替丁可通过调节轮状病毒引起的炎症反应,提高治疗总有效率,加快患儿临床症状的恢复,治疗小儿轮状病毒肠炎安全有效,值得临床推广应用.     

Protective effect of trans-resveratrol on gentamicin-induced nephrotoxicity

Reactive oxygen species (ROS) have been involved in glomerular filtration rate (GFR) reduction observed after gentamicin treatment. trans-Resveratrol (TR), a natural hydroxystilbene, has been identified to be a potent inhibitor of ROS production. The aim of this work has been to study whether TR has a protective effect on gentamicin-induced nephrotoxicity in vivo and the effect of TR on lipid peroxidation and the oxidative stress induced by gentamicin. Animals that received a daily intraperitoneal injection of gentamicin (100 mg/kg body weight) showed lower GFR and renal blood flow (RBF) and higher urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) than control rats. Rats receiving TR together with gentamicin showed higher GFR and RBF and lower NAG urinary excretion than rats receiving gentamicin alone. Moreover, renal lipid peroxidation increased in rats receiving gentamicin alone, and this increase was prevented by the administration of TR. The concentration in plasma of antioxidants was higher in the group that received TR with gentamicin than in the gentamicin and control groups. The activities of lactate dehydrogenase and alkaline phosphatase were higher in rats treated with gentamicin than in control rats and were reduced by the treatment with TR. This study demonstrates an improvement in renal function in response to the administration of TR in gentamicin-induced nephrotoxicity. At least a part of this effect of TR could be based on its antioxidant activity.     

Differential effect of NDGA on cisplatin-induced nephrotoxicity in Spargue-Dawley rats

Context: Nephrotoxicity is a highly manifested complication in cancer patients undergoing cisplatin therapy. Oxidative stress, nitrosative stress, and inflammation are the major patho-mechanisms of cisplatin-induced nephrotoxicity.

Objective: The purpose of this study was to determine the protective effect of pretreatment and post-treatment of nordihydroguaiarectic acid (NDGA) on cisplatin-induced nephrotoxicity.

Material and methods: Cisplatin-induced renal damage was accessed by biochemical estimation of nephrotoxicity markers, oxidative and nitrosative stress whereas inflammatory markers were accessed by ELISA technique.

Results and conclusion: Cisplatin administration had resulted in renal injury associated with oxidative stress, nitrosative stress as evident by increased MDA, ROS, and nitrite level with decreased antioxidants such as SOD, catalase and, glutathione. Furthermore, cisplatin treated animals exhibited a noticeable pro-inflammatory response with the substantial increase in renal levels of TNF-α, IL-1β, and IL-6 and decrease in the renal level of IL-10. NDGA pretreatment did not lead to significantly rise in oxidative stress, nitrosative stress, and inflammation along with restored the level of IL-10 in the kidney and preserved renal function. Moreover, NDGA post-treatment also presented nephroprotective effects, but the effects were not as positive as compared to NDGA pretreatment. In conclusion, these results indicate that NDGA pretreatment is renoprotective while on the other hand NDGA post-treatment is not so effective in cisplatin-induced nephrotoxicity.     

前列腺素E1对内毒素致家兔急性肺损伤的治疗效应

本实验以一次性静注大肠杆菌内毒方法复制家兔急性肺损伤模型，在实验过程中观察动物血压、血气变化及肺组织病理学改变，结果前列腺素Ｅ１治疗组轻于发病组，采用ＰＧＥ１治疗内毒素所致的急性损伤有一定疗法。     

The effect of cimetidine on antibody synthesis in vitro and in vivo

The effects of the H₂-receptor antagonist cimetidine on the antibody response of murine spleen cells to sheep red blood cells (SRBC) has been examined in vitro and in vivo. Studies failed to demonstrate any detectable effect of the drug in vitro over a wide range of concentrations (10^-12 to 10^-4M). In vivo, cimetidine stimulated IgM but not IgG responses. This effect was more marked on the secondary rather than the primary response. Low doses of cimetidine (0.5–10 mg/kg) enhanced the secondary IgM response better than higher concentrations (50–100 mg/kg).     

Dose-dependent hepatoprotective effect of emodin against acetaminophen-induced acute damage in rats

Protective effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of Ventilago madraspatana Gaertn., was evaluated against acetaminophen-induced biochemical and histological alterations in rats. Acetaminophen (2 g/kg, po) administration caused significant elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, serum bilirubin and serum protein with concomitant decrease in hemoglobin and blood sugar after 24 h of its administration. Toxicant exposure intensified the lipid peroxidation and altered glutathione status, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase as well as major cellular constituents i.e., protein, glycogen and total cholesterol in liver and kidney. Treatment of emodin (20, 30 and 40 mg/kg, po) significantly lessened the toxicity by protecting acetaminophen-induced alterations in various blood and tissue biochemical variables after 24 h of its administration. Acetaminophen administration initiated histological damage in liver. Some degree of protection was seen after emodin therapy in a dose-dependent manner. Emodin at doses of 30 and 40 mg/kg effectively reversed toxic events induced by acetaminophen as same as silymarin (50 mg/kg, po). Thus, the study concluded that emodin at a dose of 30 mg/kg (po) possesses optimum hepatoprotective ability against acetaminophen-induced toxicity.     

The effect of cimetidine on parathyroid function and histopathology in primary hyperparathyroidism

Recent evidence suggests that cimetidine given pre-operatively in primary hyperparathyroidism (1 degree HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable. To determine these possible changes we studied 38 patients with 1 degree HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre-operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques. In group I at the end of cimetidine treatment, the only change observed was a small but significant (p less than 0.05) decrease of plasma calcium (-0.77 mg/dl). Histologically, the glands of group I--compared with those of group II--showed the following findings: increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); central oedema in all the cases of group I only; increased (about 50 per cent) cellular size and intranuclear 'inclusions' in 10 out of 14 cases of group I only. It is concluded that treatment with cimetidine in 1 degree HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.     

不同密度骨髓间充质干细胞移植对家兔股骨头缺血性坏死的治疗作用

目的比较不同密度的骨髓间充质干细胞(BMSCs)移植,对实验性家兔股骨头缺血性坏死(ANFH)的治疗作用,探索合适的BMSCs移植密度。方法选取成年健康新西兰大耳白兔40只,根据BMSCs移植密度随机分为1×104(A),1×105(B),1×106(C),1×107(D),1×108(E)/ml BMSCs5组。对术后2、4、6、8周的股骨头标本,进行X-射线检查、组织学观察和图象分析。结果X-射线观察显示:随着时间的进展,各组钻孔区密度逐渐增加,A组密度增加不均,8周时,B、C、D、E组钻孔区呈现正常的骨小梁结构,A组部分钻孔区域呈现低密度腔隙。组织学观察表明:术后2周时,各组钻孔区内出现大量的成骨细胞,A组钻孔区中心为炎性细胞;8周时B、C、D、E组钻孔区内,骨小梁趋于成熟。A组钻孔区内分布有不均匀的骨小梁和骨髓组织。图像分析表明:在B、C、D、E组钻孔区内骨小梁的面积百分比值明显高于A组。结论体外培养的BMSCs移植修复ANFH时,不宜选择104以下的密度级别,应该尽可能提高移植细胞的密度。     

The effect of cimetidine treatment on suppressor T cells in duodenal ulcer patients

Changes in the suppressor T-lymphocyte activity were studied in 11 patients with duodenal ulcer during treatment with cimetidine. The drug was administered intravenously in a dose of 200 mg four times a day for a fortnight. Suppressor T-cell activity was determined by the Shou et al. method using two-stage culture before treatment, after 4 days of the treatment, just before drug withdrawal, and 2 days and 2 wk after the treatment. Suppressor T-cell activity significantly decreased soon after starting the treatment, remained low throughout the treatment, and rapidly and significantly increased following drug withdrawal.