Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-β). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the effectiveness of aliskiren treatment in patients suffering from hypertension and diabetes.

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A systematic investigation of the chemopreventive effect of sulindac (SL) in combination with either epigallocatechin gallate (EGCG) or kaempferol similar (KMP) has been carried out 1,2-dimethyl hydrazine-treated rats (DMH). Those SL combinations with KMP and EGCG have enhanced the SL activity producing greater antioxidant, anti-inflammatory, antiproliferating, and apoptotic activities in both combinations than SL alone. The chemopreventive effects of SL with both EGCG and KMP were demonstrated by a decrease in thiobaribituric acid reactive substances level, tissue nitric oxide (NO), serum, and tissue β-catenin as well as a reduction in the multiplicity of aberrant crypt foci (ACF) with alleviation in the dysplastic changes that resulted from DMH administration. Down-regulation of proliferating cell nuclear antigen (PCNA) and cyclooxygenase-2 (COX-2) were also confirmed by immunohistochemical staining. The current study paves the way for the use of sulindac combination with kaempferol or EGCG as potential chemopreventive agents against colon cancer with more effect in combination with EGCG.

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The present study aimed to explore the extent to which immunomodulators may protect against Klebsiella pneumonia lipopolysaccharide (K pn LPS) toxicity. Two immunomodulators (levamisole and DDB) were utilized in the present work. The study was carried out on male Sprague Dawley rats, and animals were divided into four groups: One group was injected with saline intraperitoneally (i.p.) and served as a control group. The other three groups were subcutaneously daily injected with repetitive doses of K pn LPS (10, 10, 20, 20 and 40 lg/kg, i.p., for 5 consecutive days). Two of these K pn LPS-injected groups were daily cotreated with either levamisole (3 mg/kg, for 5 consecutive days, p.o) or DDB (6 mg/kg, for 5 consecutive days, p.o). At the end of the experiment, the effects of the given treatment were evaluated as regarding relative spleen and thymus weights, certain hematological changes (total and differential white blood cells count (WBCs), red blood cells count (RBCs), platelet count (PLAT), hemoglobin content (Hb), bone marrow cell count, as well as the histopathological changes in each of the spleen, thymus and bone marrow. The obtained results revealed that K pn LPS induced body weight loss, splenomegaly, thymic atrophy, leukopenia and lymphocytopenia. Each of bone marrow cells count and reticulocytes and eosinophil percentages were noticeably decreased after 5 days of K pn LPS administration. Each of the utilized drugs potentiated LPS-induced lymphocytopenia and increased segmented cells. However, DDB coadministration prior to K pn LPS injection could prevent the drop in bone marrow nucleated cells count, total WBCs, reticulocytes count and eosinophils differential count restoring them to their normal ranges. The histopathological examination of thymus, spleen and bone marrow of rats treated with either of the two utilized immunomodulators confirmed the above-mentioned results. Finally, the study reveals that DDB co-administration exerts more pronounced modulatory effect on LPS-induced hematotoxicity.