Modulation by NADPH oxidase of the chronic cardiovascular and autonomic interaction between cyclosporine and NSAIDs in female rats

El-Yazbi, Ahmed F.; Ibrahim, Karim; El‐Gowelli, Hanan M.; El-Deeb, Nevine M.; El‐Mas, Mahmoud M.

doi:10.1016/j.ejphar.2017.04.016

Cited by 12 publications

(5 citation statements)

References 49 publications

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“…Slope of the linear regression fit between ΔHR and ΔMAP at different PE and SNP doses was used as a measure of BRS. Heart rate variability (HRV) analysis was performed using the available software module as described previously [ 33 ]. Cardiac autonomic activity was assessed using two time domain and two frequency domain measures.…”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction and Western blotting were performed according to a method we previously developed and optimized [ 33 , 38 – 40 ]. Briefly, the heart and brain tissue samples kept at −80°C were crushed under liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

“…After washing 4 × 5 min with 0.05% TBST and 2 × 5 min with TBS, membranes were exposed to Clarity Western ECL substrate (BioRad, Hercules, CA) for 5 min following image detection using ChemiDoc imaging system (BioRad, Hercules, CA). Band optical density was measured using ImageJ software, and a ratio of arbitrary density units was obtained for the protein band of interest and the density of the band representing total protein for p-AMPK and p-Erk1/2 after stripping and reprobing, while IL-1 β bands were normalized to actin as described previously [ 33 , 38 ] to correct variabilities in loading and sample concentration.…”

Section: Methodsmentioning

confidence: 99%

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Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

Al-Assi

Ghali

Mroueh

et al. 2018

Oxidative Medicine and Cellular Longevity

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Cardiac autonomic neuropathy (CAN) is an early cardiovascular complication of diabetes occurring before metabolic derangement is evident. The cause of CAN remains elusive and cannot be directly linked to hyperglycemia. Recent clinical data report cardioprotective effects of some antidiabetic drugs independent of their hypoglycemic action. Here, we used a rat model receiving limited daily increase in calories from fat (HC diet) to assess whether mild metabolic challenge led to CAN in absence of interfering effects of hyperglycemia, glucose intolerance, or obesity. Rats receiving HC diet for 12 weeks showed reduction in baroreceptor sensitivity and heart rate variability despite lack of change in baseline hemodynamic and cardiovascular structural parameters. Impairment of cardiac autonomic control was accompanied with perivascular adipose inflammation observed as an increased inflammatory cytokine expression, together with increased cardiac oxidative stress, and signaling derangement characteristic of diabetic cardiomyopathy. Two-week treatment with metformin or pioglitazone rectified the autonomic derangement and corrected the molecular changes. Switching rats to normal chow but not to isocaloric amounts of HC for two weeks reversed CAN. As such, we conclude that adipose inflammation due to increased fat intake might underlie development of CAN and, hence, the beneficial effects of metformin and pioglitazone.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

Al-Assi

Ghali

Mroueh

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Right kidneys were collected, frozen in liquid nitrogen, and stored at −80℃ for determination of the protein expressions of TLR‐4, MCP‐1, and NADPH oxidase‐2 (NOX2) by the Western blotting technique as described in our previous studies 65,66 . Kidneys were homogenized on ice in a radioimmunoprecipitation assay buffer (150 mmol/L NaCl, 1% Nonidet P‐40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulphate, 50 mmol/L Tris‐HCl with pH 8.0, 0.4 µL Protease Inhibitor Buffer, 2.5 µL Phosphatase Inhibitor Buffer).…”

Section: Methodsmentioning

confidence: 99%

“…The NIH image analysis software was used to read the band intensity of the target proteins against control sample after normalization in relation to β‐actin. Densitometric analysis is performed using Image software 65,66 …”

Section: Methodsmentioning

confidence: 99%

Distinct effects of calcineurin dependent and independent immunosuppressants on endotoxaemia‐induced nephrotoxicity in rats: Role of androgens

Elzokm

Fouda

Moneim

et al. 2021

Clin Exp Pharma Physio

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Evidence suggests that immunosuppressant therapies protect against harmful effects of endotoxaemia. In this study, we tested whether calcineurin‐dependent (cyclosporine/tacrolimus) and ‐independent (sirolimus) immunosuppressants variably influence nephrotoxicity induced by endotoxaemia and whether this interaction is modulated by testosterone. We investigated the effects of immunosuppressants on renal histopathological, biochemical and inflammatory profiles in endotoxic male rats and the role of androgenic state in the interaction. Six‐hour treatment of rats with lipopolysaccharide (LPS, 3 mg/kg) increased (i) serum urea/creatinine, (ii) width of proximal/distal tubules, (iii) tubular degeneration and vacuolation, (iv) Western protein expressions of renal toll‐like receptor 4, monocyte chemoattractant protein‐1, and NADPH oxidase‐2, and (v) serum tumour necrosis factor‐α and myeloperoxidase. These endotoxic manifestations were intensified and eliminated upon concurrent exposure to cyclosporine and sirolimus, respectively. The cyclosporine actions appear to be a class rather than a drug effect because similar exacerbation of LPS nephrotoxicity was observed in rats treated with tacrolimus, another calcineurin inhibitor (CNI). Moreover, the deteriorated renal outcomes in LPS/tacrolimus‐treated rats were reduced after castration or androgen receptor blockade by flutamide. The data suggest opposite effects for calcineurin‐dependent (exaggeration) and ‐independent immunosuppressants (amelioration) on renal defects of endotoxaemia and implicate androgenic pathways in the worsened endotoxic renal profile induced by CNIs.

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Role of Alcohol Oxidative Metabolism in Its Cardiovascular and Autonomic Effects

El‐Mas

Abdel‐Rahman

2019

Advances in Experimental Medicine and Biology

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Modulation by NADPH oxidase of the chronic cardiovascular and autonomic interaction between cyclosporine and NSAIDs in female rats

Cited by 12 publications

References 49 publications

Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

Distinct effects of calcineurin dependent and independent immunosuppressants on endotoxaemia‐induced nephrotoxicity in rats: Role of androgens

Role of Alcohol Oxidative Metabolism in Its Cardiovascular and Autonomic Effects

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