Pifithrin-α ameliorates glycerol induced rhabdomyolysis and acute kidney injury by reducing p53 activation

ObjectivesRhabdomyolysis is a series of symptoms caused by the dissolution of striped muscle, and acute kidney injury (AKI) is a potential complication of severe rhabdomyolysis. The underlying causes of AKI are remarkably complex and diverse. Here, we aim to investigate whether pifithrin-α protected against rhabdomyolysis-induced AKI and to determine the involved mechanisms.MethodsIntramuscular injection in the right thigh caudal muscle of C57BL/6J mice with 7.5 ml/kg saline (Group A) or of the same volume 50% glycerol was used to induce rhabdomyolysis and subsequent AKI (Group B). Pifithrin-α was injected intraperitoneally 4 h before (Group C) or 4 h after (Group D) the glycerol injection. Serum creatine kinase, blood urea nitrogen, and creatinine were determined, and the renal cortex was histologically analyzed. Renal expression levels of interested mRNAs and proteins were determined and compared, too.ResultsIntramuscular injection of glycerol induced rhabdomyolysis and subsequent AKI in mice (Groups B–D). Renal function reduction and histologic injury of renal tubular epithelial cells were associated with increased p53 activation, oxidative stress, and inflammation. Notably, compared with pifithrin-α rescue therapy (Group D), pretreatment of pifithrin-α (Group C) protected the mice from severe injury more effectively.ConclusionsOur present study suggests that p53 may be a therapeutic target of AKI caused by glycerol, and the inhibition of p53 can block glycerol-mediated AKI by using pharmacological agents instead of genetic inhibitory approaches, which further supports that p53 played a pivotal role in renal tubular injury when challenged with glycerol.     

Spinal cord involvement in Lewy body-related α-synucleinopathies

Context: Lewy body (LB)-related α-synucleinopathy (LBAS) is the neuropathological hallmark of several neurodegenerative diseases such as Parkinson disease (PD), but it is also found in neurologically asymptomatic subjects. An abnormal accumulation of α-synuclein has been reported also in the spinal cord, but extent and significance of the spinal cord involvement are still poorly defined.Objective: We aimed to review the studies addressing the spinal cord involvement of LBAS in healthy subjects and in patients with PD or other neurodegenerative diseases.Methods: A MEDLINE search was performed using following terms: “spinal cord”, “ α-synucleinopathy”, “α-synuclein”, “Lewy body”, “Parkinson’s disease”, “multiple system atrophy”, “neurodegenerative disorder”.Results: LBAS in the spinal cord is associated with that of the medullary reticular formation and locus ceruleus in the brainstem but not with that in the olfactory bulb and amygdala. The intermediolateral columns of the thoracic and sacral cord are the most frequently and severely affected region of the spinal cord. LBAS occurs in centrally projecting spinal cord neurons integrating pain, in particular from lower body periphery. It also involves the sacral parasympathetic nucleus innervating the smooth muscles of the bladder and distal colon and the Onuf’s nucleus innervating the striated sphincters. The spinal cord lesions may thus play a crucial role in the genesis of frequent non-motor symptoms such as pain, urinary symptoms, bowel dysfunction, autonomic failure including orthostatic hypotension and sexual disturbances. Moreover, these may also contribute to the motor symptoms, since α-synuclein inclusions have been observed in the pyramidal tracts of patients with PD and multiple system atrophy.Conclusion: Recognition of this peculiar spinal cord pathology may help in the management of the related symptoms in subjects affected by α-synucleinopathies.     

Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury

Ischemia is the most frequent cause of acute kidney injury (AKI), which is characterized by apoptosis of renal tubular cell. A common result of ischemia in AKI is dysfunction of endoplasmic reticulum (ER), which causes the protein-folding capacity to lag behind the protein-folding load. The abundance of misfolded proteins stressed the ER and results in induction of the unfolded protein response (UPR). While the UPR is an adaptive response, over time it can result in apoptosis when cells are unable to recover quickly. Recent research suggests that ER stress is a major factor in renal tubular cell apoptosis resulting from ischemic AKI. Thus, ER stress may be an important new progression factor in the pathology of ischemic AKI. In this article, we review UPR signaling, describe pathology and pathophysiology mechanisms of ischemic AKI, and highlight the dual function of ER stress on renal tubular cell apoptosis.     

Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA receptor antagonism in rats

Objective: The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.

Methods: Rats were subjected to bilateral renal I/R (40?min I, 24?hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin &; eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60?mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200?mg/kg), and spermidine (20?mg/kg) were administered prior to curcumin treatment in rats followed by AKI.

Results: I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.

Conclusion: It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.     

Endoplasmic reticulum oxidoreductase 1 alpha modulates prostate cancer hallmarks

BackgroundTherapies available for late stage prostate cancer (PCa) patients are limited and mostly palliative. The necessary development of unexplored therapeutic options relies on a deeper knowledge of molecular mechanisms leading to cancer progression. Redox signals are known to modulate the intensity and duration of oncogenic circuits; cues originating from the endoplasmic reticulum (ER) and downstream exocytic organelles are relevant in secretory tumors, including PCa. Ero 1α is a master regulator of redox homeostasis and oxidative folding.MethodsWe assessed Ero 1α mRNA expression by bioinformatic analysis of three public datasets and protein expression levels in PCa cell lines representing different degrees of tumor progression and different human prostate specimens. Transient Ero 1α knockdown was achieved by RNA interference (siRNA). Consequences of Ero 1α downregulation were monitored by PCa proliferation, migration and invasion properties.ResultsEro 1α mRNA and protein levels are upregulated in PCa cell lines compared to non-tumorigenic cells (P=0.0273). Ero 1α expression increases with the grade of malignancy, reaching the highest level in the androgen resistant PC3. In patients’ samples from 3 datasets, Ero 1α mRNA expression correlates with pathological Gleason scores. Ero 1α knockdown inhibits proliferation (P=0.0081), migration (P=0.0085) and invasion (P=0.0007) of PC3 cells and alters the levels of integrin β1 (P=0.0024).ConclusionsResults indicate that Ero 1α levels correlate with PCa aggressiveness; Ero 1α silencing inhibits key steps over the PCa metastatic process. Therefore, Ero 1α has the potential to be exploited as a novel biomarker and a therapeutic target in PCa.     

TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy

BackgroundIgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis.MethodsForty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks.ResultsBSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice.ConclusionTNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.     

Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury

1. Download : Download high-res image (379KB)
2. Download : Download full-size image

     

Gait analysis combined with the expression of TGF-β1, TGF-β3 and CREB during Achilles tendon healing in rat

PurposeTo observe the changes of gait behavior and the expression of wound healing factors of transforming growth factor-β1 (TGF-β1), TGF-β3 and cAMP response element binding protein-1 (CREB-1) during the healing of Achilles tendon in a rat model, and to investigate whether gait analysis can be used to evaluate the tendon healing.MethodsAchilles tendon of 40 healthy male Sprague-Dawley rats were transected and sutured to establish the Achilles tendon injury (ATI) model. They were randomly divided into 4 groups based on the observational time point at 1, 2, 4 and 6 weeks after injury (n = 10 for each group). Before modeling, 9 rats were randomly selected for CatWalk gait analysis, which contained step cycle, single stance time and average speed. Data were recorded as the normal controls. After then, ATI models were established in the left hind limbs of the all 40 rats (ATI group), while the right hind limbs were only cut and sutured without injury of the Achilles tendon (sham operation group). At 1, 2, 4 and 6 weeks after injury, the gait behavior of the corresponding group of rats (n = 9) as observed and recorded by CatWalk platform. After then, the rats were sacrificed and Achilles tendon of both limbs was harvested. The tendon healing was observed by gross anatomy and histological examination, and the protein and mRNA expression of TGF-β1, TGF-β3, CREB-1 were observed by immunohistochemistry and qPCR. The results of tendon gross grading were analyzed by Wilcoxon rank sum test, and other data were analyzed by one-way analysis of variance among multiple groups.ResultsCompared with normal controls, all gait indexes (step cycle, single stance time and average speed) were greatly affected following ATI, which however improved with time. The step cycle was significantly lower at 1, 2 and 4 weeks after ATI (compared with normal controls, all p < 0.05), but almost returned to the normal level at 6 weeks ((0.694 ± 0.102) vs. (0.503 ± 0.094) s, p > 0.05). The single stance time of the ATI group was significantly shorter at 1 and 2 weeks after operation ((0.078 ± 0.010) s at 1 week, (0.078 ± 0.020) s at 2 weeks, all p < 0.001) and revealed no significant difference at 4 weeks (p = 0.120). The average speed of ATI group at 1, 2, 4, 6 weeks was significantly lower than that in the normal control group (all p < 0.001).Gross observation showed that the grade of local scar adhesion in ATI group increased significantly at 2, 4 and 6 weeks, compared with the sham operation group (all p < 0.001). Extensive adhesion was formed at 6 weeks after ATI. The results of HE staining showed that the number of fibroblast increased gradually and arranged more orderly in ATI group at 1, 2 and 4 weeks (all p < 0.001), and decreased at 6 weeks, but it was still significantly higher than that of the sham operation group (p < 0.001). Immunohistochemistry showed that the positive expression of TGF-β1, TGF-β3, CREB-1 in ATI group was higher than that in the sham operation group at 4 time points (all p < 0.05), which reached the peak at 2 weeks after operation and decreased at 4 weeks (p = 0.002, p < 0.001, p = 0.041, respectively). The results of qPCR suggested that the mRNA expression of TGF-β1, TGF-β3, CREB-1 in ATI group was higher than that in the sham operation group at all-time points (all p < 0.05), which reached the peak at 2 weeks after operation, decreased at 4 weeks, and significantly decreased at 6 weeks (all p < 0.001).ConclusionGait behavior indexes are associated with Achilles tendon healing. The study gives an insight of TGF-β1, TGF-β3, CREB-1 changes in the coursing of Achilles tendon healing and these cytokines may be able to be used to regulate the Achilles tendon healing.     

Diagnostic Accuracy of the Synovial Fluid α‐Defensin Lateral Flow Test in Periprosthetic Joint Infection: A Meta‐analysis

ObjectivesThere is a controversy on the diagnostic reliability and accuracy of synovial fluid α‐defensin in periprosthetic joint infection (PJI). We performed this meta‐analysis to evaluate the diagnostic accuracy of the α‐defensin lateral flow test in PJI.MethodsPubMed, Embase, and the Cochrane library were systematically searched, and articles (up to January 2020) on the diagnosis of hip and knee PJIs using the α‐defensin Synovasure lateral flow test were included. The diagnostic accuracy of the α‐defensin lateral flow test in PJI was evaluated using meta‐analysis. The pooled sensitivity, specificity, accuracy, positive and negative likelihood ratio, diagnostic odds ratio, and post‐test probabilities were calculated.ResultsSeventeen studies including 1443 cases were included. Meta‐analysis showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and a diagnostic odds ratio was 0.83 (95% CI 0.77, 0.88), 0.95 (95% CI 0.93, 0.97), 16.86 (95% CI 11.67, 24.37), 0.17 (95% CI 0.13, 0.24) and 85.30 (95% CI 47.76, 152.35), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.97 (95% CI 0.95, 0.98). Subgroup analysis also confirmed the high efficiency of α‐defensin Synovasure lateral flow test in diagnosing PJIs, irrespective of ethnicity. Fagan''s nomogram analysis there was a high positive post‐test probability of 94% and a low negative post‐test probability of 15%.ConclusionsWe indicated that the α‐defensin lateral flow test had a high accuracy for diagnosing PJI. Large‐scale studies are needed to validate its significance in PJI diagnosis.     

Evaluation of autoantibodies against vimentin and α-enolase in rheumatoid arthritis patients

IntroductionRheumatoid arthritis (RA) is categorized as an autoimmune disease with a frequency of 0.2–1% worldwide. It is reported that various autoantibodies are produced in the RA population, particularly against citrullinated peptides. Among various candidate markers for RA diagnosis, the citrullinated proteins have the highest specificity and sensitivity for both diagnosis and prognosis of RA. Anti-mutated citrullinated vimentin and α-enolase constitute a new class of autoantibodies for early detection of RA.Material and methods45 serum samples and 19 synovial fluid (SF) specimens collected from RA patients were considered for American College of Rheumatology criteria and 20 serum samples and 10 SF specimens were provided from healthy subjects as a control group. To assess the quantity of anti-citrullinated protein antibodies (ACPA), anti-mutated citrullinated vimentin (MCV) and anti-α-enolase in the serum and SF of RA patients were determined by the enzyme-linked immunosorbent assay (ELISA) method. For the evaluation of disease activity and joint destruction, we used the Disease Activity Score of 28 joints based on erythrocyte sedimentation rate (ESR) Disease Activity Score 28 (DAS28). Furthermore, to measure the molecular weight of vimentin and α-enolase, electrophoresis on 10% SDS-PAGE was performed as described before.ResultsThe anti-α-enolase level among serum samples from RA patients was significantly higher than in healthy subjects (4.49 ±0.20 ng/ml vs. 0.76 ±0.12 ng/ml) (p < 0.001). There was a direct relation between α-enolase quantity and (rheumatoid factor) RF and C-reactive protein (CRP) levels. The mean ESR value in positive and negative ACPA patients was 38.2 ±22.6 mm/h and 9.2 ±5.8 mm/h respectively (p < 0.0001). The mean DAS28-ESR was 3.3. The level of anti-MCV in the serum of RA patients (244.6 ±53.3 U/ml) was higher than in serum of the healthy group (148.73 ±71.8) (p < 0.0001). The level of anti-MCV in the SF of patients was 687.5 ±148.4 U/ml.ConclusionsIn conclusion, both autoantibodies against MCV and α-enolase are two important markers that increase in serum and SF of RA patients and are specific for diagnosis of RA disease.     

Beta2‐adrenergic receptor in kidney biology: A current prospective

Beta2‐adrenergic receptor (β₂‐AR) is a G‐protein‐coupled adrenergic receptor family member, whose clinical significance has been extensively investigated in lung, cardiovascular and muscular diseases, but its role in kidney biology remains understudied. In this review, we discuss some of the recent studies, where the effect of agonist/antagonist‐mediated activation/inhibition of β₂‐AR on disease pathogenesis process was studied, and highlighted the role of β₂‐AR in kidney biology. The expression of β₂‐AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules β₂‐AR is involved in Na‐ATPase activity and transcellular Na‐transport through protein kinase‐C activation; whereas in cultured podocytes, it was associated with depolarization of the membrane. The animal studies further revealed that β₂‐AR activation by short‐acting β₂ agonists attenuated monocyte activation, pro‐inflammatory and pro‐fibrotic responses through β‐arrestin2 dependent NF‐kB inactivation in diabetic kidney disease; in contrast, activation by long‐acting β₂ agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC‐1α dependent mitochondrial biogenesis. In conclusion, the activation of β₂‐AR may present a rapidly developing therapeutic target for renal diseases.     

Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status in β-carotene 9',10'-oxygenase knockout mice

Backgroundβ-cryptoxanthin (BCX), one of the major carotenoids detected in human circulation, can protect against the development of fatty liver disease. BCX can be metabolized through β-carotene-15,15''-oxygenase (BCO1) and β-carotene-9'',10''-oxygenase (BCO2) cleavage pathways to produce both vitamin A and apo-carotenoids, respectively, which are considered important signaling molecules in a variety of biological processes. Recently, we have demonstrated that BCX treatment reduced hepatic steatosis severity and hepatic total cholesterol levels in both wide type and BCO1^–/–/BCO2^–/– double knock out (KO) mice. Whether the protective effect of BCX is seen in single BCO2^–/– KO mice is unclear.MethodsIn the present study, male BCO2^–/– KO mice at 1 and 5 months of age were assigned to two groups by age and weight-matching as follows: (I) –BCX control diet alone (AIN-93 purified diets); (II) +BCX 10 mg (supplemented with 10 mg of BCX/kg of diet) for 3 months. At 4 and 8 months of age, hepatic steatosis and inflammatory foci were evaluated by histopathology. Retinoids and BCX concentrations in liver tissue were analyzed by high-performance liquid chromatography (HPLC). Hepatic protein expressions of SIRT1, acetylated and total FoxO1, PGC1α, and PPARα were determined by the Western blot analysis. Real-time PCR for gene expressions (MCAD, SCD1, FAS, TNFα, and IL-1β gene expression relative to β-actin) was conducted in the liver.ResultsSteatosis was detected at 8 months but not at 4 months of age. Moreover, BCX supplementation significantly reduced the severity of steatosis in the livers of BCO2 KO mice, which was associated with changes in hepatic SIRT1 acetylation of FOXO1, PGC1α protein expression and PPARα protein expression in BCO2^–/– KO mice. HPLC analysis showed that hepatic BCX was detected in BCX supplemented groups, but there were no differences in the hepatic levels of retinol and retinyl palmitate (RP) among all groups.ConclusionsThe present study provided experimental evidence that BCX intervention can reduce liver steatosis independent of BCO2.     

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

Sepsis-induced acute kidney injury (AKI) is a common and life-threatening complication in hospitalized and critically ill patients and has unacceptable morbidity and mortality rates. However, effective approaches for the diagnosis and treatment of septic AKI are still lacking. Here, we demonstrated significant increases in the miR-26a-5p levels in renal tubular cells of LPS-induced septic AKI models both in vivo and in vitro. Mechanistically, we provided evidence of the involvement of NF-κB in miR-26a-5p induction. LPS treatment of renal tubular cells led to the activation of NF-κB, and inhibition of NF-κB by TPCA-1 prevented the induction of miR-26a-5p. These results indicated that NF-κB was a key upstream factor for the induction of miR-26a-5p in septic AKI. Anti-miR-26a-5p enhanced the expression of IL-6 at both the protein and mRNA levels following LPS treatment. Furthermore, our luciferase microRNA target reporter assay verified that IL-6 is a direct target of miR-26a-5p. Blocking miR-26a-5p promoted renal inflammation and worsened kidney injury. Thus, our study indicated that the miR-26a-5p/IL-6 axis can alleviate sepsis-induced acute kidney injury by inhibiting renal inflammation. This mechanism may represent a therapeutic target for septic AKI.     

Interleukin‐1β stimulates stromal‐derived factor‐1α expression in human subacromial bursa

Chemokines produced by synoviocytes of the subacromial bursa are up‐regulated in subacromial bursitis and rotator cuff disease. We hypothesized that SDF‐1α production in bursal synoviocytes may be induced by local cytokines such as interleukin IL‐1β and IL‐6. Subacromial bursa specimens were obtained from patients undergoing shoulder surgery. Bursal specimens were stained with anti‐human antibodies to IL‐1, IL‐6, and SDF‐1α by immunohistochemistry and compared to normal and rheumatoid controls. Bursal cells were also isolated from specimens and cultured. Early passaged cells were then treated with cytokines (IL‐1β and IL‐6) and SDF‐1α expression was measured by ELISA and RT‐PCR. SDF‐1α, IL‐1β, and IL‐6 were expressed at high levels in bursitis specimens from human subacromial bursa compared to normal controls. In cultured bursal synoviocytes, there was a dose‐dependent increase in SDF‐1α production in the supernatants of cells treated with IL‐1β. SDF‐1α mRNA expression was also increased in bursal cells treated with IL‐1β. IL‐6 caused a minimal but not statistically significant increase in SDF‐1α expression. SDF‐1α, IL‐1β, and IL‐6 are expressed in the inflamed human subacromial bursal tissues in patients with subacromial bursitis. In cultured bursal synoviocytes, SDF‐1α gene expression and protein production are stimulated by IL‐1β. IL‐1β produced by bursal syvoviocytes and inflammatory cells in the human subacromial bursa is an important signal in the inflammatory response that occurs in subacromial bursitis and rotator cuff disease. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1695–1699, 2011     

Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway

Sepsis-induced acute kidney injury (AKI) continues to be associated with poor outcomes in critical care patients. Previous research has revealed that tetrahydrocurcumin (THC) exerts renoprotective effects in multiple nephritic disorders by modulating inflammation and oxidative stress. However, the effects of THC on sepsis-induced AKI and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis-induced AKI, generated by cecal ligation and puncture operation, was used to investigate the protective effects of THC and the role of SIRT1. Histological manifestation and TUNEL analysis were observed to determine the severity of kidney damage. Levels of BUN, SCr, KIM-1, and UAlb/Cr were calculated to assess the renal function. Expressions of IL-1β, IL-6, and TNF-α were measured to evaluate the inflammatory response. MDA content, SOD, GSH, CAT, and GPx activities and DHE staining were analyzed to estimate the degree of oxidative stress. Protein expressions of SIRT1, Ac-p65, and Ac-foxo1 were detected to explore the underlying mechanisms. We observed that THC not only increased the survival rate, improved the kidney function and ameliorated the renal histological damage of septic mice, but also inhibited inflammatory response, prohibited oxidative stress, and prevented cell apoptosis in renal tissues in septic mice. Mechanistically, THC remarkably increased the expression of SIRT1, accompanied by decreased expressions of downstream molecules Ac-p65 and Ac-foxo1. Meanwhile, the beneficial effects of THC were clearly abolished by the SIRT1-specific inhibitor EX527. These results delineate that THC prevents sepsis-induced AKI by suppressing inflammation and oxidative stress through activating the SIRT1 signaling.Abbreviation: Ac-p65: acetylated p65; Ac-foxo 1: acetylated forkhead box O1; AKI: acute kidney injury; BUN: blood urea nitrogen; CAT: catalase; DHE: dihydroethidium; GPx: glutathione peroxidase; GSH: reduced glutathione; IL-1β: Interleukin-1 beta; IL-6: Interleukin-6; KIM-1: kidney injury molecule 1; MDA: malondialdehyde; SCr: serum creatinine; SIRT1: silent information regulator 1; SOD: superoxide dismutase; THC: tetrahydrocurcumin; TNF-α: tumor necrosis factor-alpha; TUNEL: TdT-mediated dUTP Nick-End Labeling; UAlb/Cr: urine micro albumin/creatinine.