Renoprotective effects of crocin against colistin-induced nephrotoxicity in a rat model.

Objectives: Colistin is used to treat multidrug-resistant gram-negative bacterial infections. It increases the membrane permeability of kidney cells, leading to kidney toxicity. Crocin, a carotenoid found in saffron, has anti-oxidant and nephroprotective properties. The present study aimed to explore the potential renoprotective effects of crocin against colistin-induced nephrotoxicity. Materials and Methods: Six groups of male Wistar rats were utilized: 1- Control (0.5 ml of normal saline, 10 days, IP); 2- Crocin (40 mg/kg, 10 days, IP); 3-Colistin (23 mg/kg, 7 days, IP); 4-6 Colistin (23 mg/kg, 7 days, IP)+ crocin (10, 20, 40 mg/kg, 10 days, IP). On day 11, rats were sacrificed and their blood and kidney samples were collected to measure creatinine, blood urea nitrogen (BUN), glutathione (GSH) levels, malondialdehyde (MDA), and histopathological alterations. Results: Colistin caused a significant increase in BUN, creatinine, and MDA, and a decrease in GSH compared to the control group. It also led to congested blood vessels, glomerular shrinkage, and medullary tubular degeneration. Co-administration of crocin with colistin resulted in a significant decrease in BUN and creatinine, increased GSH levels, and ameliorated the histopathological alterations compared to the colistin group. No significant difference was found between the control group and the crocin (40 mg/kg) group. Conclusion: It might be suggested that colistin can induce kidney damage by inducing oxidative stress. However, crocin shows protective effects against colistin-induced renal injury by acting as an anti-oxidant. Hence, crocin can be used as a supplement to reduce tissue and biochemical damage caused by colistin injection.

Antifatigue Effect of Asiaticoside in Mice by Attenuating Oxidative Stress.

BACKGROUND: Asiaticoside is one of the main components of triterpenoid saponins extracted from Centella asiatica. Asiaticoside has shown the effects of wound healing, osteoclastogenesis, anti-inflammatory, anti-cancer, and improving cognition in multiple human disease models. However, studies on the antifatigue effects of asiaticoside have not been explored. Therefore, the aim of this study was to investigate the potential antifatigue effect and underlying mechanism of asiaticoside administration on exhaustive exercise performance. METHODS: Male Kunming mice were divided into four groups randomly (n = 20/group). Saline (10 mL/kg) was administered to the model control group and the other three experimental groups were fed with low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) asiaticoside once/daily for 14 days. The antifatigue effect of asiaticoside on mice was estimated by analyzing changes in body weight, weight-loaded swimming time, rotating time, lactic acid, urea nitrogen, liver/muscle glycogen, serumal superoxide dismutase, superoxide dismutase and the liver tissues of hematoxylin and eosin (H&E) staining. RESULTS: The results indicated that no significant differences were observed in the body weight of each group (p > 0.05). Compared with the model control group, supplementation of asiaticoside significantly prolonged the weight-loaded swimming time and rotating time; Decreased the blood lactic acid (LA), blood urea nitrogen (BUN), and serumal malonaldehyde (MDA); And increased the content of liver/muscle glycogen and serumal superoxide dismutase levels (SOD) (p < 0.05). Furthermore, the pathological results of the liver were improved greatly. The maximal effect was observed in the medium group of 20 mg/kg. CONCLUSIONS: Asiaticoside is capable of reducing the fatigue effect by regulating energy consumption, energy metabolism and improving antioxidant activity after exercise. While there are still some shortcomings in this study, our findings provide a scientific basis for developing an asiaticoside-based antifatigue supplement.

Effects of Shenkang Decoction on Creatinine and Blood Urea Nitrogen in Chronic Renal Failure Hemodialysis Patients: A Randomized Controlled Trial.

Objective: To explore the clinical effect of Shenkang Decoction in chronic renal failure (CRF) patients with hemodialysis (HD). Methods: From November 2020 to December 2021, a total of 160 patients with CRF, who received HD, were included as the research objects, and they were divided into a reference group and a treatment group by random number table method (80 cases in each group). The former group was given basic drug treatment, and the latter group was given Shenkang decoction treatment at the same time as basic drug treatment. The renal function indexes, Traditional Chinese Medicine (TCM) syndrome scores, nutritional status, dialysis adequacy, treatment efficiency, and adverse reactions, were compared between the two groups. Results: After treatment, the patients in the treatment group had lower levels of creatinine and blood urea nitrogen, lower TCM syndrome scores, and higher levels of various nutritional status indicators than the reference group (p < 0.05). After treatment, the effective rate of the treatment group was higher compared with the reference group (p < 0.05). There was no significant difference between the two groups of dialysis adequacy index (p > 0.05). No adverse reaction was found in the two groups of patients in routine urine, blood, stool, liver, and kidney function tests, and electrocardiogram monitoring. Conclusions: Shenkang decoction applied to CRF and HD patients can significantly improve clinical symptoms and renal function, maintain a good nutritional status and little impact on dialysis adequacy, and improve life quality with significant curative effect, high safety, and little adverse reactions.

Effectiveness and safety of Jiuwei Zhenxin granules for treating generalized anxiety disorder: A randomized controlled trial.

Background: Generalized anxiety disorder (GAD) is a chronic disorder characterized by excessive, pervasive, persistent worrying that is difficult to control. Jiuwei Zhenxin granules may be safer and more effective than non-benzodiazepine anti-anxiety drugs for treating GAD. This study aimed to assess the efficacy and safety of Jiuwei Zhenxin granules alone or in combination with the benzodiazepine alprazolam. Materials and methods: A total of 710 patients were recruited from outpatient clinics and were randomly divided into two groups to receive Jiuwei Zhenxin granules (single drug group) or Jiuwei Zhenxin granules and alprazolam (combination group). The primary outcome was the response rate, which was defined as a ≥ 50% reduction from the baseline total score on the Hamilton Anxiety Scale (HAMA). Secondary outcome measures included mean changes in HAMA total score, psychological and somatic factors, Hamilton Depression Rating Scale total score, and SF-36 health survey score. Results: At 4 weeks after treatment, the single and combination treatment groups showed significant improvement in the HAMA total score and they did not differ significantly in response rate (77.58 vs. 79.17%) or rate of adverse drug reactions (16.22 vs. 16.07%). Conclusion: Jiuwei Zhenxin granules are an effective, safe, and well-tolerated treatment against GAD. Combining them with alprazolam may not significantly improve efficacy. Clinical trial registration: [www.ClinicalTrials.gov], identifier [CHICTR1800020095].

Effect of a diet based on Iranian traditional medicine on inflammatory markers and clinical outcomes in COVID-19 patients: A double-blind, randomized, controlled trial.

Introduction: SARS-CoV-2 causes severe acute respiratory syndrome prompting worldwide demand for new antiviral treatments and supportive care for organ failure caused by this life-threatening virus. This study aimed to help develop a new Traditional Persian Medicine (TPM) -based drug and assess its efficacy and safety in COVID-19 patients with major symptoms. Methods: In February 2022, a randomized clinical trial was conducted among 160 patients with a confirmed diagnosis of COVID-19 admitted to Emam Reza (AJA) Hospital in Tehran, Iran. During their hospitalization, the intervention group received a treatment protocol approved by Iran's Ministry of Health and Medical Education (MOHME), consisting of an Iranian regimen, Ficus carica; Vitis vinifera, Safflower, Cicer arietinum, Descurainiasophia seeds, Ziziphus jujuba, chicken soup, barley soup, rose water, saffron, and cinnamon spices. All patients were compared in terms of demographics, clinical, and laboratory variables. Results: One hundred and sixty COVID-19 patients were divided into two groups: intervention and control. In baseline characteristics, there was no significant difference between the intervention and control groups (p>0.05). Using SPSS software version 22, statistical analysis revealed a significant difference in four symptoms: myalgia, weakness, headache, and cough (p<0.05). During the 5-day treatment period, the control group had significantly lower C-reactive protein (p<0.05). Conclusion: While more research with a larger sample size is needed, the proposed combination appears to be effective in the treatment of symptoms as well as inflammatory biomarkers such as C-reactive protein in COVID-19 patients.Iranian registry of clinical trials (IRCT) IRCT20220227054140N1.

Detam 1 black soybean against cisplatin-induced acute ren failure on rat model via antioxidant, antiinflammatory and antiapoptosis potential.

Background and aim: Cis-Diamminedichloroplatinum (II) (Cisplatin) is one of the most synthetic anticancer drug but have several adverse effects and one of them is acute ren failure. Cisplatin can induce nephrotoxicity occur via the toxic generation of reactive oxygen species (ROS). Black soybean (Glycine max L. Merr.) has been reported contain high levels of phenolics and anthocyanins that has antioxidant activity. This study aims to determine the effect of ethanol extract of black soybean (EEBS) against cisplatin-induced nephrotoxicity in rats. Experimental procedure: Cisplatin-induced nephrotoxicity rats treated with EEBS and the blood samples taken on days 0, 9, and 18. The effects of EEBS was evaluated by determining Interferon-γ (IFN-γ), Caspase-3 (Casp-3), and Interleukin-1ß (IL-1ß) expression using immunohistochemistry (IHC), blood urea nitrogen (BUN), Uric Acid (UA) content and catalase (CAT) content in the blood plasma with colorimetric assay kit. Results and conclusion: Based on the results, EEBS treatment had successfully reduced pro-inflammatory cytokines IL-1ß and IFN-γ, and improved physiological condition by lowering BUN and UA content while increasing CAT activity. No significant effect was found in Casp-3 expression. EEBS has potential to improve acute renal failure condition through inflammatory suppression and renal function improvement.

Pharmacodynamic evaluation of the XOR inhibitor WN1703 in a model of chronic hyperuricemia in rats induced by yeast extract combined with potassium oxonate.

Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose-effect relationship.

The effects of saffron supplementation on the measures of renal function indicators: a systematic review and meta-analysis.

CONTEXT: Saffron (Crocus sativus L.) has been proposed as a potential agent to improve renal function in animal studies. But, due to insufficient evidence in human research, further investigation is needed. OBJECTIVE: To fill this knowledge gap, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of saffron supplementation on the measures of renal function indicators in adults. Renal function was assessed based on serum urea, blood urea nitrogen, and creatinine levels. METHOD AND MATERIALS: A systematic search in PubMed/Medline, Scopus, Web of Science, Embase, and Google Scholar databases was done until March 2021 using relevant keywords. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine RCTs were included in the meta-analysis, and their quality was assessed using the Cochrane risk of bias tool. RESULTS: The pooled analysis showed that saffron supplementation had no significant effect on serum urea concentrations (WMD: - 1.05 mg/dl; 95% CI - 5.1 to 3; P = 0.6, I2 = 93%, P < 0.001) and serum creatinine levels (WMD: - 0.006 mg/dl; 95% CI - 0.08 to 0.06; P = 0.8, I2 = 79%, P < 0.001) when compared to the placebo group. In the dose-response analysis, we observed a significant non-linear relationship between the duration of saffron supplementation and serum urea and creatinine levels. CONCLUSIONS: Based on our findings, Saffron supplementation had no significant effect on renal function markers, including urea and creatinine. However, further trials are required to determine the actual effect and safety of saffron intervention in human studies. PROSPERO SUBMISSION ID: 248081.

Hepatorenal Protective Effect of Fenugreek Aqueous Extract against Lead Toxicity in Experimental Rats.

In this study, aqueous extract of germinated fenugreek seeds was investigated to assess its therapeutic effect on hepatorenal lead toxicity in experimental rats. After overnight fasting, rats were injected intraperitoneally with 0.5 mL of lead acetate at a dose of 35 mg/kg body weight for five consecutive days. Animals were divided into four groups of ten rats each: normal control; untreated negative control and rats treated with 200 or 400 mg/kg body weight of the aqueous extract. Treatments were performed by intraperitoneal injection of 1mL of the extract once a day for 28 consecutive days. Results showed significant differences between treated and control groups during the whole period of the experiment. This was demonstrated by improving body weight and level of serum total protein, decreasing levels of serum ALT, AST, total bilirubin, blood urea nitrogen, and creatinine. As well, histological analysis revealed a marked reduction in inflammation and structural alterations of liver and kidney organs of fenugreek-treated rats. This hepatoprotective effect can be attributed to the anti-inflammatory, anti-oxidant and regenerative capacity of the high content of the phytochemical constituents in the extract.

Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

Effect of fish paste products, fish balls 'tsumire', intake in Sprague-Dawley rats.

The fish paste product, fish balls 'tsumire', is a traditional type of Japanese food made from minced fish as well as imitation crab, kamaboko and hanpen. Although tsumire is known as a high-protein and low-fat food, there is a lack of scientific evidence on its health benefits. Hence, we aimed to investigate the effects of tsumire intake on organ weight and biomarker levels in Sprague-Dawley rats for 84 d as a preliminary study. Six-week-old male Sprague-Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5 % dried tsumire. Throughout the administration period, we monitored their body weight and food intake; at the end of this period, we measured their organ weight and analysed their blood biochemistry. No significant differences were observed with respect to body weight, food intake, organ weight and many biochemical parameters between the two groups. It was found that inorganic phosphorus and glucose levels were higher in group II rats than in group I rats. On the other hand, sodium, calcium, amylase and cholinesterase levels were significantly lower in group II than in group I. Interestingly, we found that the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase and leucine aminopeptidase in group II were significantly lower than in group I, and that other liver function parameters of group II tended to be lower than in group I. In conclusion, we consider that the Japanese traditional food, 'tsumire,' may be effective as a functional food for human health management worldwide.

Effects of Rapid Weight Loss on Kidney Function in Combat Sport Athletes.

Even though scientific literature shows numerous heath complications and performance decrements associated with rapid weight loss (RWL), its prevalence remains exceedingly high across various combat sports. The aim of this study was to thoroughly search the existing literature to explore the influence of RWL on kidney function in Olympic and non-Olympic combat sport athletes. PubMed and Web of Science were searched for the relevant studies. Only original articles published from 2005 onwards, written in English, that included healthy males and females who prompted ~5% weight loss within a week or less, were included in the study. Retrieved studies showed that creatinine, blood urea nitrogen and urine specific gravity values were significantly increased after RWL in the majority of the included studies. This observation indicates that RWL caused dehydration and subsequent acute kidney damage despite various degrees of weight lost during the RWL phase, which can lead to adverse events in other body systems. Alternative methods of weight reduction that prioritize athletes' health should be considered.

Delayed diagnosis of atraumatic urinary bladder rupture.

Spontaneous rupture of the urinary bladder (SRUB) is a very rare and often missed diagnosis. While the clinical presentation is often non-specific, SRUB is associated with a high mortality rate and therefore warrants swift diagnosis in order to avoid delay in management. Herein, we present a case of SRUB with multiple etiological factors and temporal association with phosphate enema administration.

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics.

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases.

A reduced CP level without medicinal zinc oxide does not alter the intestinal morphology in weaned pigs 24 days post-weaning.

The use of medicinal zinc oxide (ZnO) to prevent diarrhoea post-weaning will be banned in the EU from 2022. Therefore, new alternatives are needed to avoid an increase in diarrhoea and higher antibiotic use. A low dietary CP level has shown to lower the frequency of diarrhoea in pigs, due to lower microbial protein fermentation in the colon as well as improved conditions in the small intestine after weaning. The objective of this study was to examine the effect of decreased CP levels post-weaning as an alternative to medicinal ZnO on gut morphology and histopathology. Five hundred and sixty pigs were randomly assigned into one of six groups receiving a two-phase diet from 5.5 to 15 kg: positive control group (PC) with medicinal ZnO and standard levels of protein (19.1-18.4% CP), negative control group (NC) without medicinal ZnO and standard levels of protein (19.1-18.4% CP). The remaining four low protein groups were a low-standard (LS) CP level (16.6-18.4% CP), a low-low (LL) CP level (16.6-16.2% CP), a very low-high (VLH) CP level (14-19.3% CP) and a very low-medium (VLM) CP level (14-17.4% CP). Individual BW was recorded at day 0, 10 and 24 post-weaning, and all antibiotic treatments were recorded. Tissue samples from the small intestine (mid-jejunum) for morphological and histopathologic analysis, organ weights, blood and urine samples were collected at day 10 and 24 post-weaning from a total of 90 sacrificed weaners. The results demonstrated no differences in intestinal morphology between groups, but the histopathology showed a damaged brush border score in VLM and VLH pigs . In addition, a lower blood urea nitrogen in VLM pigs at 24 days was found. The LL and VLM pigs had a significantly decreased average daily gain in the overall trial period compared to PC and NC pigs. Conclusively, intestinal brush border was damaged by the very low protein diet at 24 days post-weaning, but intestinal morphology was unaffected by dietary strategy.

Jingshu Keli for treating cervical spondylotic radiculopathy: The first multicenter, randomized, controlled clinical trial.

BACKGROUND: Jingshu Keli (or Jingshu granules), a traditional Chinese medicine, are widely used for treating cervical spondylotic radiculopathy in China; however, no randomized, double-blind, controlled study has verified their effectiveness. PURPOSE: To evaluate the efficacy and safety of Jingshu Keli for the treatment of cervical spondylotic radiculopathy in a randomized controlled trial. DESIGN: From August 2015 to July 2017, a multicenter, randomized, double-blind, placebo-controlled trial was conducted at 13 large- and medium-sized hospitals in China. PATIENT SAMPLE: A total of 360 and 120 patients were initially enrolled in the Jingshu and control groups, respectively; 386 patients completed the study, with 299 in the Jingshu group and 87 in the control group. OUTCOME MEASURES: The main index for evaluating the curative effect was the pain score on a visual analogue scale (VAS; 0-100 points). METHODS: All patients were administered a bag of Jingshu Keli or placebo 3 times a day for 4 weeks, and were interviewed at the second and fourth weeks. The decrease in pain scores and rate of change in pain scores after treatment were calculated, related laboratory indices were reviewed, and adverse reactions were recorded. RESULTS: In the Per Protocol Set (PPS) analysis, the baseline pain VAS scores in the control and Jingshu groups were 49.31 â€‹± â€‹6.97 and 50.06 â€‹± â€‹7.33, respectively, with no significant difference between the groups (P â€‹> â€‹0.05). While there were no differences at 2 weeks between groups, at four weeks the pain VAS scores in the control and Jingshu groups decreased by 12.86 â€‹± â€‹13.45 and 22.72 â€‹± â€‹15.08, respectively relative to the values at baseline, with significant group differences (P â€‹< â€‹0.0001). While there were similar significant differences between the groups (P â€‹< â€‹0.0001) in the Full Analysis Set (FAS) analyses neither group achieved the minimal clinically important difference at any time point. CONCLUSIONS: Jingshu Keli are effective for the treatment of cervical spondylotic radiculopathy. TRANSLATIONAL POTENTIAL STATEMENT: This is the first prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial that confirmed the clinical efficacy and safety of Jingshu Keli for treating cervical spondylotic radiculopathy, which can provide evidence for clinical treatment.

Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy.

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX-S-DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu2+) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.

Protective Effect of Croton macrostachyus (Euphorbiaceae) Stem Bark on Cyclophosphamide-Induced Nephrotoxicity in Rats.

BACKGROUND: Cyclophosphamide is an alkylating antineoplastic agent and its major limitation is injury to normal tissue, leading to multiple organ toxicity, including kidney, heart, liver and reproductive toxicity. Croton macrostachyus (Euphorbiaceae) has been used in Ethiopian traditional medicine to manage renal diseases. OBJECTIVE: The present study aims to assess the protective effect of the stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced using cyclophosphamide 200 mg/kg i.p injection on the first day of the experiment. The negative control groups were administered with cyclophosphamide alone (200 mg/kg, i.p.). The crude extracts were administered at three dose levels (100, 200, and 400 mg/kg), while aqueous and ethyl acetate fractions were given at two dose levels (100 and 200 mg/kg). Excepting the normal control, all groups were subjected to cyclophosphamide toxicity on the first day. RESULTS: Treatment with crude extract 100 mg/kg and ethyl acetate fraction significantly decreased kidney-to-body weight ratio (P < 0.001). In addition, treatment with Croton macrostachyus crude extract and solvent fractions significantly decreased serum blood urea nitrogen (BUN) level (P < 0.001). Treatment with 100 and 200 mg/kg of ethyl acetate fraction significantly decreased serum creatinine level. Histopathological results confirmed the protective effect of the crude extract and solvent fractions of Croton macrostachyus. CONCLUSION: Croton macrostachyus possesses nephroprotective activities and it could be a possible source of treatment for cyclophosphamide-induced nephrotoxicity.

[Effects of early supplement of exogenous L-carnitine on renal function in severely scalded rats].

Objective: To explore the effects of early exogenous L-carnitine supplementation on renal function in severely scalded rats. Methods: According to the random number table, sixty-six adult female Sprague-Dawly rats were divided into healthy control group (n=6), scald alone group (n=30), and scald+ carnitine group (n=30). In the latter two groups, the rats were inflicted with full-thickness scald of 30% total body surface area on the back, and the lactated Ringer's solution was injected through the tail vein for resuscitation immediately after scald. At post injury hour (PIH) 1, rats in scald+ carnitine group were intraperitoneally injected with 100 mg/mL L-carnitine solution 400 mg/kg, while rats in scald alone group were intraperitoneally injected with the same volume of normal saline. Rats in these two groups were injected once every 24 hours thereafter. Six rats were taken from each of scald alone group and scald+ carnitine group to collect the renal tissue and abdominal aorta blood at PIH 6, 12, 24, 48, and 72, respectively. The serum content of total protein, albumin, urea nitrogen, creatinine, and cystatin C were determined by the automatic biochemical analyzer. Renal tissue was stained with hematoxylin-eosin to observe histopathological changes. Rats in healthy control group did not undergo any treatment, and their renal tissue and blood sample were extracted and analyzed in the same way as those of severely scalded rats. Data were statistically analyzed with one-way analysis of variance and Bonferroni method. Results: (1) The serum content of total protein and albumin of rats in scald alone group at each time point after injury was significantly lower than that in healthy control group (P<0.05). The serum content of total protein of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 and 24 (P<0.05), and the serum content of albumin of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 (P<0.05). The serum content of total protein and albumin of rats in scald alone group and scald+ carnitine group showed a trend of decrease followed by an increase, with the lowest value at PIH 24. (2) The serum content of urea nitrogen and creatinine of rats in scald alone group at each time point after injury was significantly higher than that of healthy control group (P<0.05). The serum content of urea nitrogen of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 6, 48, and 72 (P<0.05). The serum content of creatinine of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 12, 24, 48, and 72 (P<0.05). The serum content of urea nitrogen and creatinine of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (3) The serum content of cystatin C of rats in scald alone group at PIH 6, 12, 24, 48, and 72 was (0.250±0.030), (0.330±0.070), (0.300±0.060), (0.240±0.060), and (0.190±0.030) mg/L, and the content at the first 4 time points were significantly higher than (0.170±0.020) mg/L of healthy control group (P<0.05). At PIH 24, the serum content of cystatin C of rats in scald+ carnitine group was (0.210±0.040) mg/L, which was significantly lower than that of scald alone group (P<0.05). The serum content of cystatin C of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (4) The renal tissue of rats in healthy control group was almost normal, and the degree of renal tissue injury of rats in scald+ carnitine group was lighter than that in scald alone group at each time point after injury. At PIH 24, the renal tissue of rats in scald alone group showed extensive swelling of the renal tubular epithelial cells, vacuolar degeneration and necrosis, loss of brush borders, and nuclear shrinkage; more than 2/3 of the renal tubular cell nuclei disappeared, the tubular lumen was narrowed, necrotic exfoliated cells could be seen in the lumen, and edema and inflammatory cell infiltration could be seen in the renal interstitial. Compared with those of scald alone group, significantly reduced severity of edema and necrosis of renal tubular epithelial cells, as well as less inflammatory cell infiltration were observed in the renal tissue of rats in scald+ carnitine group. Conclusions: Early supplement of L-carnitine in severely scalded rats can reduce the damage of renal cells, accelerate the restoration of the content of total protein, albumin, urea nitrogen, creatinine, and cystatin C, thereby maintaining the stability of renal function metabolism level.