scholarly journals Melatonin mitigates cisplatin-induced acute kidney injury through regulation of the heat shock proteins expressions

Author(s):  
Ali Tuğrul Akin ◽  
Murat Unsal ◽  
Tayfun Ceylan ◽  
Emin Kaymak ◽  
Emel Ozturk ◽  
...  

Abstract Purpose. To determine the protective effects of melatonin (MEL) in acute kidney injury (AKI) induced by Cisplatin (CP), widely used as a chemotherapeutic in the treatment of many cancer types, via assessment of heat-shock proteins (HSPs) levels in rats. Methods. Total 40 Wistar albino rats were divided into four groups: Control (n = 10), MEL (n = 10, 10 mg/kg/i.p melatonin for 8 days), CP (n = 10, 7 mg/kg/i.p cisplatin at the 5th day), and CP + MEL (n = 10, 10 mg/kg/i.p melatonin for 8 days and 7 mg/kg/i.p cisplatin at the 5th day). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and glomerular and tubular immunoreactivities of HSP47, HSP60, HSP7, and HSP90 in renal cortex were detected by immunohistochemistry. Moreover, blood serum BUN, creatinine and uric acid levels were measured to assess of kidney function. Results. CP group showed histopathological deterioration compared to Control group and MEL treatment attenuated this damage. When compared with Control and MEL groups, an increase in HSPs immunoreactivities in renal cortex and blood serum BUN, creatinine and uric acid levels were observed in the CP group. Furthermore, an improvement was observed in the CP + MEL in terms of these parameters compared to the CP group. Conclusion. According to our results, MEL could exert a significant protective effect to ameliorate CP-induced AKI via regulation of heat-shock protein expressions.

2018 ◽  
Vol 35 (6) ◽  
pp. 23-28
Author(s):  
M. O. Ivanov ◽  
N. M. Ivanova ◽  
M. V. Maksimenya ◽  
T. M. Karavaeva ◽  
E. V. Egorova ◽  
...  

Aim. To determine the content of heat shock proteins with molecular weight 70 kDa (HSP 70) and antibo dies to them in blood and nasal secretion in patients with allergic rhinites and infectious rhinosinusites of different etiology. Materials and methods. The paper presents the results of examination of 10 patients with allergic rhinitis and 30 patients, infected with rhinosinusites(the age range 25–35 years). The patients with infectious rhinosinusites were divided into 3 groups according to nosologic form of disease. The control group included 10 practically healthy persons in the ratio, comparable by their gender and age with sick persons. Results.The analysis showed that in the nasal secretion of all patients, HSP 70 level significantly raised compared to the control. Maximum values were registered in patients with bacterial rhinosinusitis and were higher than in patients with viral and fungous ones by 1.9 times (p = 0.015) and 2.9 times (p = 0.001), respectively. In blood serum, HSP 70 concentration compared with the control increased in patients with allergic rhinitis and bacterial rhinosinusitis by 103.67 % (p = 0.015) and 32.11 % (p = 0.049), respectively; these values in the last two groups exceeded the latter in patients with fungous RS by 2.37 times (p = 0.01) and by 1.54 times (p = 0.035). Conclusions. It was detected that in the group of patients with allergic rhinitis and chronic bacterial rhinosinusitis in the nasal secretion and blood serum, HSP 70 values were the highest. In the nasal secretion, HSP 70 level was higher than in blood. The amount of autoantibodies to HSP 70 in blood grew in allergic rhinitis, fungous and viral forms of rhinosinusites that reflects the immunological effect of chaperone proteins.


2001 ◽  
Vol 281 (3) ◽  
pp. H1346-H1352 ◽  
Author(s):  
Karyn L. Hamilton ◽  
Scott K. Powers ◽  
Takao Sugiura ◽  
Sunjoo Kim ◽  
Shannon Lennon ◽  
...  

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups ( n = 12/group): 1) control, 2) exercise (60 min/day) at 4°C (E-Cold), and 3) exercise (60 min/day) at 25°C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher ( P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/d t), and pressure relaxation over time (−dP/d t) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher ( P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts ( P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.


2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Hu ◽  
Tian Ye ◽  
Yanzhen Yang ◽  
Ben Liu ◽  
Wenya Zheng

Abstract Background Transportation is necessary to introduce new breeds of goats to the farm and move the adult meat goat from the farm to the slaughterhouse. However, these actions may give rise to transport stress. Heat shock proteins (HSPs) are playing some important regulate roles during transport stress. The aim of this study was to evaluate the effects of transport stress on the pathological injury and HSPs expression in the stomach of goats. A total of three batches of Ganxi goats from western Jiangxi province were enrolled in this study. For each batch, twelve healthy adult male goats were randomly divided into three groups (four goats per batch and per group): Control group, stress group transported during 2 h and stress group transported during 6 h. Results Our results showed that the different degrees of stomach walls damage, with the change of expression levels of heat shock protein 27 (HSP27), heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90), occurred after goats transportation. In rumen, the mRNA and protein expressions of HSP27 and HSP70 were increased after transport stress, but not HSP90. In reticulum, all three HSPs mRNA and protein levels were upregulated after 2 h transport, but decreased after 6 h transport. In omasum, HSP27 and HSP70 mRNA and protein were increased after transport stress, however, HSP90 mRNA level only had a slightly enhancement after transport stress. In abomasum, HSP70 and HSP90 mRNA and protein levels were increased after transport stress, but HSP27 was decreased after transport stress. Conclusions Taken together, these results revealed that the pathological changes in the gastric tissues and the stomach HSPs expression in goats are related to transport stress and duration. Moreover, this study also provides some new data to advocate reducing transport stress of goats and improving animal welfare.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2403-2403
Author(s):  
Yunfeng Cheng ◽  
Yong Tang ◽  
Neal S. Young

Abstract Heat shock proteins (HSP) have been implicated in autoimmune diseases such as type I diabetes mellitus, systemic lupus erythematosus, and multiple sclerosis, in which T cell proliferative responses or autoantibodies towards endogenous HSP have been detected (Journal of Autoimmunity2003;20:313). HSP70 can function as an endogenous ‘danger’ signal, acting on antigen-presenting cells and critically influencing the decision between induction of tolerance and immunity upon antigen encounter (Millar et al. Nature Medicine2003; 9:1469). We studied T-cell proliferative responses and auto-antibodies to human HSP60, HSP70 and HSP90 proteins in 20 newly diagnosed aplastic anemia patients, peripheral blood was obtained (11 females, 9 males; age average 36.1±19 years). A non-isotopic immunoassay was used for BrdU incorporation into proliferative T cells and ELISA to measure HSP antibody titer. T cell proliferation was measured as the Eu-fluorescence in a time-resolved fluorometer. A positive result was defined as > 2 standard deviations (SD) from the mean of the controls. T-cell responses to HSP70 in the patient group (N=20; mean±SD Eu-fluorescence= 47,129±36,248) were significantly greater than those of the control group (N=18 healthy adult; mean Eu-fluorescence= 23,941±12,996; p=0.01). Fifty percent of the patients showed increased T cell proliferation after HSP70 stimulation compared to 5% in the control group (p=0.03). T-cell responses of the patient group to HSP90 and HSP60 were similar to those of the control group. Twenty percent of patients showed increased T cell proliferation to HSP 60 and HSP 90 stimulation compared to 5% in the control group (p=0.363). HSP antibody (IgG/A/M) seropositivity was 25% to HSP60, 50% to HSP70, and 5% to HSP90 in patients and 8% to HSP60, 0% to HSP70, and 0% to HSP90 in controls. Heightened autoimmunity to HSP70, but not to HSP60 and HSP90, is a feature of acquired aplastic anemia at presentation.


2016 ◽  
Vol 4 (3) ◽  
pp. 114-117 ◽  
Author(s):  
Shobhana Nayak Rao

AbstractHeat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Shinichiro Watanabe ◽  
Takashi Kawano ◽  
Taro Horino ◽  
Tatsuki Matsumoto ◽  
Keitaro Nagata ◽  
...  

Abstract Objective Hyperuricemia has been reported to be associated with the development of postoperative acute kidney injury (pAKI). However, it remains underdetermined whether hyperuricemia treatment could decrease the potential risk of pAKI. Here, we investigated this hypothesis among hyperuricemia patients with previously normal renal function by performing a retrospective database analysis. Results The study screened 18,169 patients, and were examined preoperative serum creatinine, uric acid, and postoperative serum creatinine. Eight hundred thirty-six patients were finally analyzed for the study, of whom 232 were in the treatment group and 604 were in the non-treatment control group. After adjustment for multi-covariates including baseline (pre-treatment) serum uric acid (SUA) levels, the incidence of pAKI in the treatment group (9.05%; 95% CI 6.04–12.1%) was significantly lower than that in the control group (14.2%; 95% CI 11.2–17.2%). On the other hand, further adjusting for preoperative SUA levels, there was no significant difference in the expected incidence of pAKI between the groups.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ender Hur ◽  
Alev Garip ◽  
Asuman Camyar ◽  
Sibel Ilgun ◽  
Melih Ozisik ◽  
...  

Introduction. Acute kidney injury (AKI) pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI.Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im) daily; Genta group, gentamicin 100 mg/kg/day (im); Genta + vitamin D, gentamicin 100 mg/kg/day (im) in addition to 1α, 25 (OH)2D30.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed.Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups.Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.


2014 ◽  
Vol 116 (11) ◽  
pp. 1463-1472 ◽  
Author(s):  
Noni T. Frankenberg ◽  
Graham D. Lamb ◽  
Kristian Overgaard ◽  
Robyn M. Murphy ◽  
Kristian Vissing

Small heat shock proteins (sHSPs) are a subgroup of the highly conserved family of HSPs that are stress inducible and confer resistance to cellular stress and injury. This study aimed to quantitatively examine whether type of contraction (concentric or eccentric) affects sHSPs, HSP27 and αB-crystallin, localization, and phosphorylation in human muscle. Vastus lateralis muscle biopsies from 11 healthy male volunteers were obtained pre- and 3 h, 24 h, and 7 days following concentric (CONC), eccentric (ECC1), and repeated bout eccentric (ECC2) exercise. No changes were apparent in a control group ( n = 5) who performed no exercise. Eccentric exercise induced muscle damage, as evidenced by increased muscle force loss, perceived muscle soreness, and elevated plasma creatine kinase and myoglobin levels. Total HSP27 and αB-crystallin amounts did not change following any type of exercise. Following eccentric exercise (ECC1 and ECC2) phosphorylation of HSP27 at serine 15 (pHSP27-Ser15) was increased approximately 3- to 6-fold at 3 h, and pαB-crystallin-Ser59 increased ∼10-fold at 3 h. Prior to exercise most of the sHSP and psHSP pools were present in the cytosolic compartment. Eccentric exercise resulted in partial redistribution of HSP27 (∼23%) from the cytosol to the cytoskeletal fraction (∼28% for pHSP27-Ser15 and ∼7% for pHSP27-Ser82), with subsequent full reversal within 24 h. αB-crystallin also showed partial redistribution from the cytosolic to cytoskeletal fraction (∼18% of total) 3 h post-ECC1, but not after ECC2. There was no redistribution or phosphorylation of sHSPs with CONC. Eccentric exercise results in increased sHSP phosphorylation and translocation to the cytoskeletal fraction, but the sHSP translocation is not dependent on their phosphorylation.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4191-4191
Author(s):  
Jaroslaw Piszcz ◽  
Edyta Cichocka ◽  
Lukasz Bolkun ◽  
Marzenna Galar ◽  
Katarzyna Mazgajska-Barczyk ◽  
...  

Abstract Background: Chronic lymphocytic leukaemia (CLL) is one of the diseases in which processes of proliferation and apoptosis are altered. It has been intensely studied in the recent years in order to understand the mechanisms of neoplastic development. Hsps or heat shock proteins are molecular chaperones involved in a number of cellular functions in stress conditions. Feng et al. (2002) have reported that heat-stressed apoptotic 12B1-D1 leukaemia cells (BCR-ABL(+)) express Hsp70 on their surface. It has also been suggested that an increased surface expression of heat shock proteins on apoptotic tumour cells results in the generation of potent antitumour T-cell responses. Furthermore, different hsps including Hsp70 have been discovered in indolent lymphoma cells. Anti Hsp70 antibodies are known to play a role in immunological and neoplastic processes. It has been well documented that this antibodies level tends to increase with age likewise an incidence of CLL. However their significance in CLL has not been clearly understood. Aims: The aim of our study was the assessment of the anti Hsp70 antibody concentration in the patients with CLL. Material and methods: We assessed 60 peripheral blood samples from the patients with newly diagnosed CLL. (aged 40–77), including 31 males and 29 females. A group of 20 healthy age matched subjects were used as a control group. The patients were in A-C stages of CLL according to Binet scale. Quantitative determination of anti-human Hsp70 antibodies in the serum was done using commercial test (anti Hsp70 Elisa Kits, Stressgen). The results are presented as mean ± SEM. Statistical analysis was done using Shapiro-Wilk, Mann-Whitney and Spearman’s tests. Results: The levels of anti Hsp70 antibodies were significantly lower in the group of patients with CLL in comparison to healthy controls (105,70±16,86 ng/ml vs.243,71±60,36 ng/ml; p=0,0027). In our analysis there was no association between the levels of antibodies and the stage of the disease. There were no statistically significant correlations between the levels of anti Hsp antibodies and other parameters such as age, gender and some prognostic factors (LDH, β2-microglobulin, and lymphocyte doubling time) in the studied group. Conclusions: The significantly lower concentrations of anti Hsp70 antibodies in CLL patients suggest that these molecules may play a role in the biology of the disease. Our study revealed lack of correlation between the level of antibodies and the disease prognostic factors. However, further studies utilizing new discovered factors are required to elucidate the role of these proteins in leukaemic biology. The encouraging results from our study suggest that it might be interesting to assess their level in CLL patient after chemotherapy.


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