مقالات  دکتر زهرا صداقت  


  Hind limb per-conditioning renoprotection by modulation of inflammatory cytokines after renal ischemia/reperfusion Renal Failure 2016 ISI, PubMed .” Zahra Sedaghat, Mehri Kadkhodaee, Behjat Seifi, Eisa Salehi
Purpose Renal ischemia/reperfusion (I/R) injury is a common clinical problem associated with significant mortality and morbidity. One newly described strategy to reduce this damage is remote perconditioning (RPEC), in which short-time ischemia of a limb during renal ischemia reduces the I/R-induced kidney injury. This study aimed to assess whether RPEC confer protection through changes in pro-inflammatory mediators. Methods Rats were subjected to right nephrectomy and randomized into: sham (no intervention), I/R (subjected to 45-min left renal ischemia) and RPEC group (subjected to four cycles of 5-min I/R of the femoral artery administered during renal ischemia). After 24-h, blood, urine, and kidney samples were collected. Biochemical indicators of renal dysfunction were measured in the cases of Neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-B-diglucosaminidase (NAG) activity. Inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor-alpha, TNF-α] expression in the renal tissues as well as Periodic acid-Schiff stained histological sections were evaluated. Results I/R resulted in renal dysfunction, as evidenced by higher renal NGAL expression and urinary NAG activities. This was accompanied by increased TNF-α and IL-6 expressions as well as histological changes in this group. However, RPEC improved renal histology and function compared with the I/R group. Furthermore, the RPEC group showed decreases in TNF-α and IL-6 expression. Conclusions These results suggest that RPEC reduces the dysfunction and injury associated with I/R of the kidney. This technique reduced the pro-inflammatory cytokine in the kidney. RPEC could be a promising strategy against I/R-induced acute kidney injury partly by down-regulation of inflammatory mediators.
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  Postconditioning is protective in renal reperfusion injury only in male rats. A gender difference study Acta Physiol Hung 2015 ISI, PubMed Mahmoudi A1, Kadkhodaee M1, Golab F2, Najafi A3, Sedaghat Z4
PURPOSE: We investigated the impact of sex on the protective effect of postconditioning (POC), a series of brief ischemia-reperfusion (IR) cycles at the reperfusion onset, as a recently described novel approach to attenuate renal IR injury. In this study, the left renal pedicles of uni-nephrectomized male and female rats were clamped for 45 minutes followed by 24 hours of reperfusion as IR groups. Uni-nephrectomized, sham-operated male and female rats served as control groups. Ischemic postconditioning was performed using 4 cycles of 10 seconds of IR of renal pedicle at the end of the ischemia. Twenty-four hours later, BUN (blood urea nitrogen), plasma creatinine (Cr), and renal histological changes, as well as kidney levels of MDA (malondialdehyde) and SOD (superoxide dismutase) as oxidative stress markers were evaluated to detect the protective effect of POC against IR injury in rats. RESULTS: Induction of IR resulted in significant reduction in renal function, demonstrated by increase in plasma Cr and BUN, histological changes and oxidative stress in both genders. Application of POC afforded significant protection against these injuries in male rats, namely decreased levels of BUN and Cr, histological improvements and less oxidative damages. However, there were no significant differences in the above-mentioned parameters in female rats. CONCLUSION: While POC is shown to be beneficial against renal IR injury in male rats, it did not show any protective effect in female rats.

  Angiotensin II in paraventricular nucleus contributes to sympathoexcitation in renal ischemia-reperfusion injury by AT1 receptor and oxidative stress. J Surg Res. 2015 ISI, PubMed Seifi B, Kadkhodaee M, Bakhshi E, Ranjbaran M, Zahmatkesh M, Sedaghat Z, Ahghari P, Esmaeili P
. BACKGROUND: To investigate the effect of angiotensin II (Ang II) in the hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion (IR) injury and to assay the role of renal sympathetic nerve activity (RSNA). METHODS: A cannula was inserted into the right side PVN in Sprague-Dawley rats for microinjection of Ang II (3, 30, and 300 ng); Ang II AT1 receptor antagonist, losartan (0.3 μg); and the superoxide dismutase (SOD) mimetic, tempol (20 nmol) before right side nephrectomy. After 1 wk, renal IR injury was induced by clamping the left renal artery for 45 min, and then reperfusion for 3 or 24 h. The extent of renal damage was determined by evaluation of renal functional indices. RSNA was recorded in all groups. Oxidative stress indices (SOD activity and malondialdehyde levels) were assayed in the PVN. RESULTS: Microinjection of pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3 ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished by pretreatment with tempol. CONCLUSIONS: These results indicate that the PVN is a responsive site for central Ang II increment damage in renal ischemia-reperfusion injury. We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by AT1 receptors and oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway.

  ارزيابي روند بهبود آسيب کليوي ناشي از ايسکمي و پرفيوژن مجدد در موش صحرايي با استفاده از دستگاه اسپکت حيوانات کوچک دم ماه نامه طب جنوب سال بيست و دوم، شماره 2 ISC زهرا صداقت، حسین فاطمی کیا، کاوه تنها، ماریا ظهیری، مجید اسدی، خلیل پورخلیلی، بهجت سیفی اول از هفت نفر
Background: Renal injuries associated with ischemia/reperfusion are a prevalent clinical phenomenon that can cause the emergence of progressive kidney diseases, eventually leading to chronic kidney injuries. The present study was conducted to evaluate the results obtained from non-invasive imaging using small-animal SPECT and investigate the recovery process in an animal model of renal ischemia/reperfusion. Materials and Methods: Male Wistar rats were used to establish a unilateral model of renal ischemia/ reperfusion injury. After occluding the left renal pedicle for 120 minutes, the animals were investigated in terms of reperfusion at 24 hours, one week and three weeks. At each time point, the intravascular injection of 99mTc-DMSA as well as scanning with the SPECT machine were conducted. Blood sampling and renal biopsy were also performed. Results: After 24 hours, the accumulated activity levels were significantly lower in the ischemic kidney compared to in the contralateral intact kidney. Severe renal histologic changes were also observed. After one and three weeks, the radiopharmaceutical uptake increased in the ischemic compared to both the contralateral kidney and the time point of 24 hours, and the absorbed activity was divided between the two kidneys in a more balanced fashion, which is quite consistent with the histologic results. Conclusion: The present findings suggest that non-invasive imaging with a small-animal SPECT system using 99mTc-DMSA provides researchers with an appropriate tool in rodent models of renal ischemic damage for evaluating the long-term follow-up of kidney recovery. The obtained results also appear to be thoroughly consistent with invasive histological studies

http://ismj.bpums.ac.ir/article-1-1068-fa.html&sw=%D8%B5%D8%AF%D8%A7%D9%82%D8%AA
  Inducible and endothelial nitric oxide synthase distribution and expression with hind limb per-conditioning of the rat kidney Arch Med Sci 2019; 15 (4): 1081–1091 ISI Zahra Sedaghat, Mehri Kadkhodaee, Behjat Seifi, Eisa Salehi اول از 4 نفر
Introduction: We recently reported that a series of brief hind limb ischemia and reperfusion (IR) at the beginning of renal ischemia (remote per-conditioning – RPEC) significantly attenuated the ischemia/reperfusion-induced acute kidney injury. In the present study, we investigated whether the nitric oxide synthase (NOS) pathway is involved in the RPEC protection of the rat ischemic kidneys. Material and methods: Male rats were subjected to right nephrectomy and randomized as: (1) sham, no additional intervention; (2) IR, 45 min of renal ischemia followed by 24 h reperfusion; (3) RPEC, four 5 min cycles of lower limb IR administered at the beginning of renal ischemia; (4) RPEC+L-NAME (a non-specific NOS inhibitor, 10 mg/kg, i.p.) (5) RPEC + 1400W (a specific iNOS inhibitor, 1 mg/kg, i.p.). After 24 h, blood, urine and tissue samples were collected. Results: The protective effect of RPEC on renal function, oxidative stress indices, pro-inflammatory marker expression and histopathological changes of kidneys subjected to 45 min ischemia were completely inhibited by pretreatment with L-NAME or 1400W. It was accompanied by increased iNOS and eNOS expression in the RPEC group compared with the IR group. Conclusions: These findings suggest that the protective effects of RPEC on renal IR injury are closely dependent on the nitric oxide production after the reperfusion and both eNOS and iNOS are involved in this protection.
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https://www.termedia.pl/Inducible-and-endothelial-nitric-oxide-synthase-distribution-and-expression-with-hind-limb-per-conditioning-of-the-rat-kidney,19,36849,1,1.html
  Scintigraphic evaluation of remote preconditioning protection against unilateral renal ischemia/reperfusion injury in rats: a longitudinal study International Urology and Nephrology (2019) 51:2083-2089 ISI ISI Zahra Sedaghat· Hossein Fatemikia · Kaveh Tanha · Maria Zahiri · Majid Assadi اول از 5 نفر
Purpose To determine the role of remote perconditioning (RPeC) on renal function and histology in an animal model of unilateral renal ischemia and reperfusion (IR) injury. Methods Rats were subjected to 60 min unilateral renal ischemia. RPeC protocol was the application of four cycles of 5 min IR of left femoral artery during renal ischemia. Assessments of histological changes and renal function were made 24 h, 1 week, or 3 weeks later. 99mTc-DMSA scan was performed using a small-animals SPECT system. Results 24-h reperfusion decreased the 99mTc-DMSA uptake in the left kidney compared to the intact kidney of control animals. RPeC group has higher uptake compared to the IR group. After 1 week and 3 weeks, uptakes were gradually increased in both groups and no differences were observed. Severe morphological changes in the ischemic kidneys of both groups were observed after 24 h which attenuated after 1 week and 3 weeks. Moreover, no differences in creatinine and BUN levels between IR-treated and intact animals were observed. Conclusion These data suggest that RPeC exerts a partially transient improvement in the renal function in the first day after reperfusion. However, long-term follow-up study showed no beneficial effects of RPeC. Moreover, noninvasive 99mTc-DMSA scan revealed a suitable tool in the follow-up evaluation of recovery process in the unilateral renal IR injury models.
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https://link.springer.com/article/10.1007%2Fs11255-019-02258-3

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