The therapeutic prospect of zinc oxide nanoparticles in experimentally induced diabetic nephropathy.

Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was to evaluate the prospective efficacy of ZnO-NPs in treating DN in streptozotocin-induced diabetic rats. Rats were randomly dispersed into three sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were processed for biochemical analyses. Kidney samples were managed for light and electron microscopy studies. Immune histochemical staining of P53, aquaporin11 (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs ameliorated the functional and histopathological alterations of the kidney in a rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the glomerular filtration barrier and restored almost normal renal structure. This was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and podocin) and AQP11 immune histochemical expression in the renal tubules. The beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic potential (evidenced by the decrease in p53 immune expression), anti-inflammatory and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-κB) level and blood hypoxia-inducible factors (HIF-1α) level]. These results may point the way to an effective therapy of DN.Abbreviations: AQP11 Aquaporin11; BUN: Blood urea nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3'-diaminobenzidine; DM: Diabetes mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; H&E: Hematoxylin & eosin; HIF-1α: Hypoxia-inducible factors; iNOS: inducible nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: Mechanistic target of rapamycin; NF-κB: Nuclear factor kappa beta; NPs: Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X ± SEM: Mean ± standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.

Efficacy of platelet rich plasma on pancreatic injury induced by renal ischemia reperfusion in adult male rats.

Renal ischemia-reperfusion (I-R) injury is the main cause of acute renal failure. Acute pancreatitis is one of the fatal remote lesions that occurs in patients with renal I-R injury. Platelet-rich plasma (PRP) is a hopeful aiding therapy for tissue injuries. Forty adult rats were utilized in this study, ten for PRP preparation and thirty were divided into three groups; Control: subdivided into three equal subgroups, I-R group: exposed to bilateral renal pedicles clamping and I-R+ PRP group: were experienced identical procedures as I-R group then subcutaneously (S.C) injected with 0.5 ml PRP two times weekly for three weeks. Blood samples were taken for detection of serum urea and creatinine, blood glucose level and serum amylase. The pancreas was dissected and prepared for histopathological examination by light and electron microscope. Statistical analysis of all collected results was performed. Our biochemical results revealed deleterious effects of renal I-R on the pancreas as evidenced by a highly significant increase in serum amylase and blood glucose level. In I-R group, histopathological examination revealed wide septa and congested blood vessels, acinar cells showed disrupted rough endoplasmic reticulum and few secretory granules. Some islet cells showed pyknotic nuclei and vacuolated cytoplasm. PRP treated group showed nearly normal structure in the form of numerous acinar cells' granules, extensive rough endoplasmic reticulum and mitochondria. Most of Beta cells had euchromatic nuclei and numerous secretory granules. Accordingly, PRP treatment reduced the pancreatic biochemical and histopathological alterations caused by renal I-R injury and so considered a promising therapy for pancreatic damage.

Ameliorative effect of zinc oxide nanoparticles on cyclophosphamide induced testicular injury in adult rat.

Despite its wide range of application, cyclophosphamide (CP) exhibits a wide range of adverse effects including reproductive toxicity. The emerging field of zinc oxide nanoparticles (ZnO NPs) therapy may provide a new hope for prevention of CP induced gonadal toxicity. Herein, we aim to investigate the possible role of ZnO NPs as a new strategy to protect against CP induced testicular injury. Sixty adult male albino rats were divided into 3 groups; control, CP treated and CP + ZnO NPs treated groups. CP group was injected with CP (5 mg/kg/day), whereas CP + ZnO NPs group was concomitantly injected with CP and ZnO NPs (5 mg/kg/day). Testicular specimens were processed for histological, ultrastructural and c-kit immunohistochemical study. Biochemical analysis for tissue malondialdehyde and serum testosterone was done in addition to sperm morphology assay and cytogenetic study. Our results revealed that CP induced deleterious testicular histopathological, biochemical and genetic alterations that were effectively prevented by ZnO NPs.

Molecular mechanisms underlying histological and biochemical changes induced by nitrate in rat liver and the efficacy of S-Allylcysteine.

This study was designed to investigate structural and ultra-structural changes induced by nitrate in rat liver, examine their molecular basis, and evaluate the possible protective role of S-Allylcysteine (SAC). Adult male albino rats were assigned to: control, SAC, nitrate, and nitrate+ SAC groups. Serum ALT and AST were measured. Liver samples were processed for light and electron microscope examinations, biochemical analysis, real-time PCR, and immunohistochemistry of heat shock protein 70 (HSP70) and Bcl-2. Nitrate induced histopathological and biochemical alterations in rat liver. The underlying mechanisms included nitrosative and oxidative stress, inflammation, fibrosis, and apoptosis that are alleviated by SAC.

Therapeutic effect of mesenchymal stem cells on experimentally induced hypertensive cardiomyopathy in adult albino rats.

Hypertensive heart diseases affect millions of people worldwide. We aimed to investigate the hypertensive left ventricular histological changes and assess the effectiveness of bone marrow derived mesenchymal stem cells (MSCs) therapy in the treatment of hypertensive cardiomyopathy. Adult male albino rats were assigned into two groups: group I (control), group II (Experimental) subdivided into subgroup IIa (hypertensive) and subgroup IIb (stem cell therapy). Left ventricles (LVs) were processed for light and electron microscope. Mallory's trichrome and immunostaining for caspase-3 and desmin were carried out. Hypertension caused left ventricular histological and immunohistochemical changes that had been effectively improved by MSCs therapy.