Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO- decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.

AbstractDiabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages. In vitro, EPA abrogates cardiomyocyte injury induced by M1-polarized macrophages, switching macrophage phenotype from M1 to Mox, but not M2, polarization. Moreover, macrophage Mox polarization combats M1-polarized macrophage-induced cardiomyocyte injury. Further, heme oxygenase 1 (HO-1) was identified to maintain the Mox phenotype, mediating EPA suppression of macrophage M1 polarization and the consequential cardiomyocyte injury. Mechanistic studies reveal that G-protein-coupled receptor 120 mediates the upregulation of HO-1 by EPA. Notably, EPA promotes Mox polarization in monocyte-derived macrophages from diabetic patients. The current study provides EPA and macrophage Mox polarization as novel strategies for DC intervention.

Vinorelbine, the standard chemotherapy drug on advanced lung cancer, causes adverse events such as immunosuppression and bone marrow suppression. Thus, it is necessary to find drugs that could improve immune function and synergistically enhance the anti-tumor effect of vinorelbine. Thymosin is reported to inhibit tumor growth as an immunomodulator. Herein, to study the synergistic anti-cancer and attenuation effects of thymosin on vinorelbine, human lung cancer A549 cells that were labeled with CM-DiI were transplanted into zebrafish to establish the lung cancer xenotransplanted model. After treatment of vinorelbine and different concentrations of thymosin, the fluorescence intensity of CM-DiI-labeled A549 cells and the number of apoptotic muscle cells in the tumor-bearing zebrafish were detected. Besides, effects of thymosin on vinorelbine-reduced macrophages and T cells were identified in the transgenic zebrafish (Tg:zlyz-EGFP and Tg:rag2-DsRed). Then, the qRT-PCR was used to determine the alterations of the immune-related factors at the transcription level. Thymosin showed a marked synergistic anti-cancer effect with vinorelbine for the xenograft human lung cancer A549 cells, and the synergistic effect enhanced in a dose-dependent manner. Moreover, thymosin alleviated vinorelbine-induced muscle cell apoptosis, macrophage reduction, and T cell suppression. Compared with the vinorelbine group, co-administration with thymosin raised the mRNA levels of TNF-α, TNF-β, INF-γ, and GM-CSF. Thus, thymosin possesses synergistic anti-cancer effect on vinorelbine, and has protective effect on vinorelbine-induced immunosuppression. Thymosin, as an adjuvant immunomodulatory therapy, has great potential in enhancing the clinical application of vinorelbine.

It is generally considered that protein supplementation and resistance exercise significantly increase muscle mass and muscle growth. As the hydrolysis products of proteins, peptides may play the crucial role on muscle growth. In this study, male rats were orally administrated 0.4 g/kg body weight of pea peptide combined with 8 weeks of moderate intensity resistance exercise training. After treatment, the body gains, upper limb grip, muscle thickness, and wet weight of biceps brachii were tested, and the cross-sectional area of biceps brachii muscle fiber and the types of muscle fibers were determined by HE staining, immunofluorescence staining, and lactate dehydrogenase activity, respectively. Western blot analysis was used to investigate the level of growth-signaling pathway-related proteins. The results showed that pea peptide supplementation combined with resistance exercise training significantly increased body weight, upper limb grip, muscle thickness, wet weight of biceps brachii, and cross-sectional area of muscle fiber. Meanwhile, pea peptide supplementation obviously elevated the ratio of fast-twitch fiber (type II) and the expression of muscle growth-signaling pathway-related proteins. In addition, the PP2 oligopeptide in pea peptide with the amino acid sequence of LDLPVL induced a more significant promotion on C2C12 cell growth than other oligopeptides.

Purpose:The prevalence of hyperlipidemia and related illnesses is on its rise, and atorvastatin is the frequently used hypolipidemic agent.However, there is still uncertainty about the mechanisms, especially the relationship between the lipid-lowering effect, intestinal microbiome, and metabolic profiles.We aim to intensively explain the mechanism of the hypolipidemic effect of atorvastatin through multi-omics perspective of intestinal microbiome and metabolomics.Methods: Multi-omics methods play an increasingly important role in the analysis of intestinal triggers and evaluation of metabolic disorders such as obesity, hyperlipidemia, and diabetes.Therefore, we were prompted to explore intestinal triggers, underlying biomarkers, and potential intervention targets of atorvastatin in the treatment of dyslipidemia through multi-omics.To achieve this, SPF Wistar rats were fed a high-fat diet or normal diet for 8 weeks.Atorvastatin was then administered to high-fat diet-fed rats.Results: By altering intestinal microbiome, a high-fat diet can affect feces and plasma metabolic profiles.Treatment with atorvastatin possibly increases the abundance of Bacteroides, thereby improving "propanoate metabolism" and "glycine, serine and threonine metabolism" in feces and plasma, and contributing to blood lipid reduction.Conclusion: Our study elucidated the intestinal triggers and metabolites of high-fat diet-induced dyslipidemia from the perspective of intestinal microbiome and metabolomics.It equally identified potential intervention targets of atorvastatin.This further explains the mechanism of the hypolipidemic effect of atorvastatin from a multi-omics perspective.

Katsuwonus pelamis peptide and its complexes have the effect of lowering uric acid (UA)-levels. To identify the effect and possible mechanisms, different concentrations of Katsuwonus pelamis peptide and its complexes were administered to the zebrafish and mice hyperuricemia models, and the UA level was measured. Meanwhile, the hyperuricemic mice were treated orally at 0.83, 1.67, and 5.00 mg/g body weight for 7 days with Katsuwonus pelamis peptide and the complexes groups, separately. The levels of serum UA (SUA), urinary UA (UUA), serum creatinine (SCR), blood urine nitrogen (BUN), and xanthine oxidase (XOD) activities were detected in each group. The results showed that the Katsuwonus pelamis peptide (125 μg/ml) and its complexes (83.3 and 250 μg/ml) effectively reduced UA level in zebrafish with hyperuricemia (p < 0.05). The Katsuwonus pelamis peptide at high concentration (5.00 mg/g) decreased the SUA level, SCR level, BUN level, and hepatic XOD activity, and the complexes (1.67 and 5.00 mg/g) significantly reduced the SUA level and hepatic XOD activity (p < 0.05) in the hyperuricemic mice. In addition, in a hyperuricemic mouse model, the UUA level was increased after treatment with Katsuwonus pelamis peptide and its complexes at high concentrations (p < 0.05). The total therapeutic effects in the Katsuwonus pelamis peptide complex group were better than those in the Katsuwonus pelamis peptide group. Thus, Katsuwonus pelamis peptide and its complexes may possibly be used to prevent hyperuricemia via promoting urate secretion and inhibiting XOD activity production.

Objective. To investigate the effects of mung bean peptide and its’ complexes on promoting lead excretion and neuroprotection of zebrafish. Methods. The lead poisoning models of zebrafish were established by lead acetate solution; the models were treated with high and low concentrations (58.3 and 175 μg/mL) of mung bean peptides, with high, medium, and low concentrations (27.8, 83.3, and 250 μg/mL) of mung bean peptide complexes, separately. The effects of the mung bean peptide complexes on the lead content, axonal fluorescence intensity, and peripheral motor nerve length changes were identified in the zebrafish model, and the effects of mung bean peptide and its’ complexes on zebrafish's lead excretion, axonal protection rate, and peripheral movement promotion rate of nerve regeneration were calculated. Results. The effects of high concentration of mung bean peptide (175 μg/mL) in promoting lead excretion was 29% ( p < 0.05 ), and the effect of high concentration of mung bean peptide complexes (250 μg/mL) in promoting lead excretion was 30% ( p < 0.05 ). The other concentrations of mung bean peptide and its’ complex groups did not show a noticeable lead excretion effect. The protective effects of mung bean peptide at concentrations of 58.3 and 175 μg/mL against zebrafish axonal injury were 98% and 101% ( p < 0.01 ), and the peripheral nerve regeneration promotion effects were 29% ( p > 0.05 ) and 42% ( p < 0.05 ), respectively. The protective effects of mung bean peptide complexes at concentrations of 27.8, 83.3, and 250 μg/mL against zebrafish axonal injury were 85%, 78%, and 93% ( p < 0.01 ); peripheral nerve regeneration promotion rates were 46%, 50%, and 50% ( p < 0.05 ). Conclusion. The mung bean peptide and its’ complexes can effectively promote the discharge of lead in the zebrafish lead poisoning and have protective and regeneration effects on zebrafish nerves.

Objective: To assess the effect of flavonoids on chronic prostatitis, a meta-analysis of randomized controlled trials was performed. Methods: Through using subject word and random word, PubMed, Scopus, Web of Science, and Cochrane Library were searched for related records up to July 2018. The response rate and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) were used to evaluate the therapeutic efficacy of the flavonoids. The Cochrane handbook for systematic reviews of interventions version was used to evaluate the quality of included studies. The model of determining odds ratio (OR) was chose according to the value of I-2. Results: A total of 11 studies involving 975 subjects (experiment 516, control 459) were included. The overall OR of response rate was 0.31 (95%CI 0.11-0.89. P = 0.03). At the subgroup analysis, the OR of response rate of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) was 0.57 (95%CI 0.18-1.77, P = 0.33), while the OR of response rate of chronic bacterial prostatitis (CBP) was 0.08 (95% CI 0.02-0.33, P = 0.0005). The OR of response rate of CP/CPPS (control was placebo) was 0.29 (95%CI 0.16-0.52, P < 0.0001). The overall OR of baseline NIH-CPSI was -0.1 (95%0-0.61-0.41, P = 0.70). The overall OR of posttreatment NIH-CPSI was -6.96 (95%CI -8.32 similar to -5.60, P < 0.00001). Conclusions: This meta-analysis indicates that the flavonoids may be clinically beneficial through significantly improving the response rate and NIH-CPSI in chronic prostatitis patients and short-lasting antibiotics therapy in association with the flavonoids could be a better choose for CBP. Moreover, the flavonoids therapy has an excellent safety profile with minor adverse effects.

目的 建立大鼠丙烯酰胺(Acrylamide,ACR)神经中毒模型和钙蛋白酶抑制剂Calpeptin(CP)干预模型,探讨CP对ACR诱导的大脑微管(Microtubules,MT)损伤的干预作用及其机制,以期为ACR诱导的神经损伤提供预防与治疗的理论依据.方法 将40只SPF级雌性Wistar大鼠随机分为对照组、CP组、ACR组和ACR+CP组,每组10只.采用腹腔注射进行ACR染毒和CP干预,对照组给予生理盐水;CP组给予200 μg/kg CP;ACR组给予30 mg/kg ACR;ACR+CP组在给予30 mg/kg ACR后1h,给予200 μg/kg CP进行干预.每周3次,共4周.每周末进行大鼠体重、步态评分和转棒试验测定.处理结束后,迅速分离大脑组织,测定钙蛋白酶Calpain的活力,采用凝胶电泳(SDS-PAGE)和免疫印迹法(Western blot)分析α-tubulin、β-tubulin、CDK5、p25和p35蛋白的含量.结果 与对照组相比,ACR组自第三周开始步态评分升高、转棒试验停留时间缩短(P＜0.05);与ACR组相比,ACR+CP组上述变化均有所改善(P＜0.05).至实验结束时与对照组相比,ACR组Calpain活力升高了59.86％(P＜0.05);与ACR组相比,ACR+CP组Calpain活力降低了32.80％(P＜0.05).与对照组相比,CP组CDK5和p35的含量呈现升高趋势,分别升高了31.01％和19.06％ (P＜0.05),ACR组α-tubulin、β-tubulin、CDK5、p25和p35分别升高了12.63％、21.14％、52.81％、40.58％和25.05％(P＜0.05),ACR+CP组CDK5和p35的含量呈现升高趋势,分别升高了42.80％和22.60％(P＜0.05).与ACR组相比,ACR+CP组α-tubulin、β-tubulin、CDK5、p25和p35分别降低了13.10％、10.96％、6.55％、12.79％和25.65％(P＜0.05).结论 CP对ACR诱导的MT损伤具有干预作用,其机制可能是CP通过Calpain调节p35-CDK5/p25通路来维持MT的稳定性.

Abstract Background: Published studies about passive smoking and cervical cancer have found inconsistent results. Hence, the present meta-analysis was performed to assess this association. Methods: A systematical search was performed to identify eligible cohort and case–control studies in PubMed, Scopus, Elsevier ScienceDirect, and Web of Science databases (up to March, 2018). The quality of included studies was assessed by the Newcastle–Ottawa quality scale (NOS). The random effects model (REM) was used to calculate the pooled odds ratio (ORs). Subgroup and sensitivity analyses were performed. Publication bias was assessed by funnel plot, using Begg's test and Egger's test. Results: Around 14 eligible studies were included for analysis, which included a total of 384,995 participants. The pooled ORs of passive smoking with cervical cancer risk was 1.70 (95% CI: 1.40–2.07, I 2 = 64.3%). Subgroups stratified by continent, study design, quality score, and cervical cancer types/phases suggested that the result was robust. For instance, the pooled ORs for the cohort and case–control studies was 1.37 (95% CI: 1.16–1.62, I 2 = 0%) and 2.09 (95% CI: 1.52–2.89, I 2 = 76.6%), respectively. The pooled ORs ranged from 1.61 (95%CI: 1.34–1.92) to 1.77 (95%CI: 1.44–2.16) after one study was removed each time in the sensitivity analyses, indicating that the result was stable. Publication bias was detected by funnel plot and Egger's tests. The recalculated ORs were 1.33 (95% CI: 1.21–1.47). Conclusions: This meta-analysis provides evidence that passive smoking is associated with an increased risk of cervical cancer.

Zoledronic acid (ZA) exerts complex influence on bone by suppressing bone resorption, mostly due to the direct osteoclasts inhibition and uncertain influence on osteoblasts. Vitamin K2 (VK2, Menaquinone-4) as an anabolic agent stimulates bone formation via anti-apoptosis in osteoblasts and mild osteoclasts inhibition. Based on these knowledge, the therapeutic effect of the combined or sequential therapy of VK2 and ZA depends on the influence on the osteoblasts, since both cases exert similar inhibitory effect on osteoclasts. In a series of in vitro studies, we confirmed the protective effect of VK2 in osteoblasts culture, especially when followed by exposure to ZA, and the proliferation and mineralization inhibition induced by ZA towards osteoblasts. For mechanism study, expression of bcl-2/bax, Runx2 and Sost in cells were examined. For in vivo studies, an osteoporosis animal model was established in rats via ovariectomy (OVX) and subjected to sequential treatment, namely VK2 followed by ZA. Bone mineral density (BMD) was measured by Dual energy X-ray absorptionmetry (DEXA), morphology and mechanical parameters by micro-computed tomography (micro-CT), mechanical strength by an electro-hydraulic fatigue-testing machine. The bone calcium, hydroxyproline content, blood lipids were evaluated using microplate technique, and the bone surface turnover was evaluated using the fluorescence in corporation method. It was found that VK2 pretreatment partially prevented the inhibition of bone formation caused by ZA, which was reflected by indices like BMD, bone calcium content and bone strength. The underling mechanisms for protection of VK2 pretreatment, mainly demonstrated via in vitro studies, included inhibiting apoptosis and depressing Sost expression in osteoblasts, which in turn improved the osteoporosis therapeutic effects of ZA. These findings suggested that pretreatment with VK2 before ZA therapy might serve a new long-term therapy protocol for osteoporosis.

Background: Published studies about passive smoking and cervical cancer have found inconsistent results. Hence, the present meta-analysis was performed to assess this association. Methods: A systematical search was performed to identify eligible cohort and case-control studies in PubMed, Scopus, Elsevier ScienceDirect, and Web of Science databases (up to March, 2018). The quality of included studies was assessed by the NewcastleOttawa quality scale (NOS). The random effects model (REM) was used to calculate the pooled odds ratio (ORs). Subgroup and sensitivity analyses were performed. Publication bias was assessed by funnel plot, using Begg's test and Egger's test. Results: Around 14 eligible studies were included for analysis, which included a total of 384,995 participants. The pooled ORs of passive smoking with cervical cancer risk was 1.70 (95% CI: 1.40-2.07, I-2=64.3%). Subgroups stratified by continent, study design, quality score, and cervical cancer types/phases suggested that the result was robust. For instance, the pooled ORs for the cohort and case-control studies was 1.37 (95% CI: 1.16-1.62, I-2=0%) and 2.09 (95% CI: 1.52-2.89, I-2=76.6%), respectively. The pooled ORs ranged from 1.61 (95% CI: 1.34-1.92) to 1.77 (95% CI: 1.44-2.16) after one study was removed each time in the sensitivity analyses, indicating that the result was stable. Publication bias was detected by funnel plot and Egger's tests. The recalculated ORs were 1.33 (95% CI: 1.21-1.47). Conclusions: This meta-analysis provides evidence that passive smoking is associated with an increased risk of cervical cancer.

The present study aimed to investigate the protective effect and mechanism of calpeptin (CP) on acrylamide (ACR)-induced microtubule (MT) injury in the sciatic nerve of rats. All rats were divided into four groups (control, CP, ACR, and ACR + CP):1 ml/kg saline, 200 mu g/kg CP, 30 mg/kg ACR, and 30 mg/kg ACR plus 200 mu g/kg CP were administered to the corresponding rats for 4 weeks through intraperitoneal injection. Body weight and neurobehavioral indicators were measured weekly and alpha-tubulin, beta-tubulin, and other concerned proteins were estimated by western blotting and immunohistochemistry. At 4 weeks, decreased body weight, increased gait scores, increased hindlimb splay, and decreased time of fall of ACR rats were observed compared with those of control rats. All these mentioned changes were restored in the ACR + CP group compared with the ACR group. After 4 weeks of administration, western blotting and immunohistochemistry revealed significant increase in the protein levels of beta-tubulin, calpain I, calpain II, Tau, microtubule-associated protein 2 (MAP2), protein kinase C, and cyclin-dependent kinase 5 in the ACR group compared with the control group; these increases were significantly lower in the ACR + CP group than in the ACR group. Furthermore, histopathological examination revealed loose arrangement, disorganised structure, uneven density, and exfoliated perineurium in the ACR group, and CP administration improved these changes significantly. The present results suggest that CP has an intervening effect on ACR-induced MT injury. A possible mechanism is that calpain maintains the stability of MTs by regulating the metabolism of Tau and MAP2.

Understanding is emerging about microRNAs as mediators in the regulation of white adipose tissue (WAT) and obesity. The expression level of miR-199a in mice was investigated to test our hypothesis: miR-199a might be related to fat accumulation and try to find its target mRNA, which perhaps could propose strategies with a therapeutic potential affecting the fat storage. C57/BL6J mice were randomly assigned to either a control group or an obesity model group ( n =10 in both groups). Control mice were fed a normal diet (fat: 10 kcal %) ad libitum for 12 weeks, and model mice were fed a high-fat diet (fat: 30 kcal %) ad libitum for 12 weeks to induce obesity. At the end of the experiment, body fat mass and the free fatty acids (FFAs) and triglycerides (TGs) in WAT were tested. Fat cell size was measured by hematoxylin-eosin (H&E) staining method. The fat mass of the model group was higher than that of the control group ( P <0.05). In addition, the concentrations of the FFAs and TGs were higher ( P <0.05) and the adipocyte count was lower ( P <0.05) in the model group. We tested the expression levels of miR-199a and key adipogenic transcription factors, including peroxisome proliferator activated receptor gamma2 (PPARγ2), CCAAT/enhancer binding proteins alpha (C/EBPα), adipocyte fatty acid-binding protein (aP2), and sterol regulatory element binding protein-1c (SREBP-1c). Up-regulated expression of miR-199a was observed in model group. Increased levels of miR-199a was accompanied by high expression levels of SREBP-1c. We found that the 3’-UTR of SREBP-1c mRNA has a predicted binding site for miR-199a. Based on the current discoveries, we suggest that miR-199a may exert its action by binding to its target mRNA and cooperate with SREBP-1c to induce obesity. Therefore, if the predicted binding site is confirmed by further research, miR-199a may have therapeutic potential for obesity.Abbreviations WAT, white adipose tissue; PPARγ2, peroxisome proliferator, activated receptor γ2; C/EBP αCCAAT/enhancer binding proteins α; aP2, adipocyte fatty acid-binding protein; SREBP-1c, sterol regulatory element binding protein-1c; HFD, high-fat diet.

The aim of this study is to explore the potent neuroprotective effect of calpeptin (CP) on neuron damage induced by acrylamide (ACR) and its mechanism. Behavioural indicators such as hind limb splay, rota-rod performance, and gait analysis were assessed weekly to evaluate neurobehavioural changes after ACR and/or CP administration. The histopathological alterations and the changes of-calpain, m-calpain, microtubule-associated protein 2 (MAP2), and alpha-tubulin and beta-tubulin protein levels in spinal cord were determined. Results showed that after administration of 30 mg/kg ACR, decreased body weight, attenuated neurobehavioural function, injury of motor neuron, increased protein levels of m-calpain and beta-tubulin, suppressed MAP2 protein level, and no significant changes of mu-calpain and a-tubulin protein levels were observed compared with the control group rats. After administration of 200 mu g/kg CP, partially restored body weight and neurobehavioural function, improvement of motor neuron injury, decreased protein levels of m- calpain and beta-tubulin, and reversed effects of MAP2 protein level were observed compared with the ACR group rats. Our results suggested that CP alleviates neuropathy induced by ACR in rats. The calpain's overactivation causes the degrading of MAP2 and eventually leads to the destruction of microtubules (MTs), which may be one of the mechanisms of cytoskeletal damage induced by ACR.

It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival. Furthermore, the underlying mechanism was explored through cell biology assays, including clonogenic survival, homologous recombination (HR) activity, immunoblot and immunofluorescence. We found that VPA and HU cooperatively suppressed cancer cell survival. VPA resulted in the accumulation of more DNA double-strand breaks (DSBs) in response to HU-induced replication arrest and was able to block HU-stimulated homologous recombination (HR) through inhibiting the activity of two key HR repair proteins by hyperphosphorylation of replication protein A2 (RPA2-p) and recombinase Rad51. However, apoptosis was not detected under this condition. In addition, the results from the survival fraction in the cells expressing defective RPA2-p showed that VPA disrupted the HU-induced RPA2-p-Rad51-mediated HR pathway. Importantly, these findings were further supported by analyzing primary-culture cells from the tissue of chemical carcinogen (DMBA)-induced breast cancer in rats. Thus, our data demonstrated that VPA and HU synergistically suppressed tumor cells via disturbing RPA2-p-mediated DNA repair pathway, which provides a new way for combining chemotherapeutic drugs to sensitize breast cancer cells.

Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group, while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and 9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs degradation. The changes of calpain activity and NFs may be one of the mechanisms of ACR-induced neuropathy.