Ameliorative Effect of Curcumin Nanoparticles against Monosodium Iodoacetate-Induced Knee Osteoarthritis in Rats.

Aim: This study is aimed at evaluating the use of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-loaded PLGA NPs) as a treatment against monosodium iodoacetate- (MIA-) induced knee OA. Materials and Methods: Eighteen rats were assigned to three groups (n = 6), namely, normal control group that received intra-articular injections (IAIs) of saline, an OA control group that received an IAIs of MIA (2 mg/50 µL), and a treatment group (MIA+CUR-loaded PLGA NPs) that received IAIs of CUR-loaded PLGA NPs (200 mg/kg b.wt). Results: The CUR NP treatment against knee OA alleviated radiographic alternations and histopathological changes and inhibited the upregulation in the serum levels of interleukin-1ß, tumor necrosis factor-α, interleukin-6, and transforming growth factor-beta and the downregulation in interleukin-10. CUR NP-treated joints also decreased the mRNA expression of nuclear factor-kappa B and inducible nitric oxide synthase and the protein expression of matrix metalloproteinase-13 and caspase-3. Finally, CUR-loaded PLGA NP treatment mitigated the loss of type II collagen, which resulted in a significant reduction in malondialdehyde level and increased the glutathione content and superoxide dismutase activity compared with that of the OA group. Conclusion: This study demonstrated that the administration of CUR NPs could provide effective protection against MIA-induced OA and knee joint histological deteriorated changes due to its anti-inflammatory, antioxidant, and antiapoptotic properties.

Thyme Oil and Thymol Counter Doxorubicin-Induced Hepatotoxicity via Modulation of Inflammation, Apoptosis, and Oxidative Stress.

Doxorubicin (DOX) is an effective anticancer agent with a wide spectrum of activities. However, it has many adverse effects on various organs especially on the liver. Thymol, one of the major components of thyme oil, has biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to examine thyme oil and thymol for their ability to prevent doxorubicin-induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced by an intraperitoneal injection of doxorubicin, at a dose of 2 mg/kg bw/week, for seven weeks. Doxorubicin-injected rats were supplemented with thyme oil and thymol at doses 250 and 100 mg/kg bw, respectively, four times/week by oral gavage for the same period. Treatment of rats with thyme oil and thymol reversed the high serum activities of AST, ALT, and ALP and total bilirubin, AFP, and CA19.9 levels, caused by doxorubicin. Thyme oil and thymol also reduced the high levels of TNF-α and the decreased levels of both albumin and IL-4. These agents ameliorated doxorubicin-induced elevation in hepatic lipid peroxidation and associated reduction in GSH content and GST and GPx activities. Further, the supplementation with thyme oil and thymol significantly augmented mRNA expression of the level of antiapoptotic protein Bcl-2 and significantly downregulated nuclear and cytoplasmic levels of the hepatic apoptotic mediator p53. Thus, thyme oil and thymol successfully counteracted doxorubicin-induced experimental hepatotoxicity via their anti-inflammatory, antioxidant, and antiapoptotic properties.

Curcumin and Mesenchymal Stem Cells Ameliorate Ankle, Testis, and Ovary Deleterious Histological Changes in Arthritic Rats via Suppression of Oxidative Stress and Inflammation.

Rheumatoid arthritis (RA) is a chronic inflammatory condition, an autoimmune disease that affects the joints, and a multifactorial disease that results from interactions between environmental, genetic, and personal and lifestyle factors. This study was designed to assess the effects of curcumin, bone marrow-derived mesenchymal stem cells (BM-MSCs), and their coadministration on complete Freund's adjuvant- (CFA-) induced arthritis in male and female albino rats. Parameters including swelling of the joint, blood indices of pro-/antioxidant status, cytokines and histopathological examination of joints, and testis and ovary were investigated. RA was induced by a single dose of subcutaneous injection of 0.1 mL CFA into a footpad of the right hind leg of rats. Arthritic rats were treated with curcumin (100 mg/kg b.wt./day) by oral gavage for 21 days and/or treated with three weekly intravenous injections of BM-MSCs (1 × 106 cells/rat/week) in phosphate-buffered saline (PBS). The treatment with curcumin and BM-MSCs singly or together significantly (P < 0.05) improved the bioindicators of oxidative stress and nonenzymatic and enzymatic antioxidants in sera of female rats more than in those of males. Curcumin and BM-MSCs significantly (P < 0.05) improved the elevated TNF-α level and the lowered IL-10 level in the arthritic rats. Furthermore, joint, testis, and ovary histological changes were remarkably amended as a result of treatment with curcumin and BM-MSCs. Thus, it can be concluded that both curcumin and BM-MSCs could have antiarthritic efficacies as well as protective effects to the testes and ovaries which may be mediated via their anti-inflammatory and immunomodulatory potentials as well as oxidative stress modulatory effects.

Polydatin and polydatin-loaded chitosan nanoparticles attenuate diabetic cardiomyopathy in rats.

Hyperglycemia is associated with impairment of heart function. The current study aimed to investigate the ameliorative effect of polydatin-loaded chitosan nanoparticles (PD-CSNPs), polydatin (PD) and metformin (MET) on diabetic cardiomyopathy in rats. Rats divided into six groups; normal-control, diabetic-control, diabetic + CSNPs (diabetic rats treated with 50 mg/kg blank chitosan nanoparticles), diabetic + PD-CSNPs (diabetic rats treated with PD-CSNPs equivalent to 50 mg/kg of polydatin), diabetic + PD (diabetic rats given 50 mg/kg polydatin), diabetic + MET (diabetic rats given 100 mg/kg metformin), orally and daily for 4 weeks. Treatment of diabetic rats with PD-CSNPs, PD and MET showed a significant reduction in the values of glucose and glycosylated hemoglobin with improvement in heart function biomarkers through decreasing serum creatine kinase and creatine kinase myocardial band activities compared to diabetic control. The treatment agents also suppressed the elevated lipid peroxidation product, increased values of glutathione content, superoxide dismutase, superoxide peroxidase, and catalase activities in the heart of diabetic treated rats. Furthermore, PD-CSNPs, PD and MET decreased heart tissue levels of a pro-inflammatory cytokine; tumor necrosis factor-alpha and nuclear factor-kappa ß, upregulation of heart gene expressions; nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. Histological and ultrastructural examinations revealed the ameliorative effect of PD-CSNPs, PD and MET against the harmful of diabetic cardiomyopathy by reducing the cardiac fibers, necrotic cardiac myocytes, inflammatory cell infiltration, and the arrangement of the myofibrils and intercalated discs. In conclusion, the new formula of PD-CSNPs was more effective than PD and MET in amelioration the diabetic cardiomyopathy through its antioxidant, anti-inflammatory and prolonged-release properties.

Hesperidin protects against chemically induced hepatocarcinogenesis via modulation of Nrf2/ARE/HO-1, PPARγ and TGF-ß1/Smad3 signaling, and amelioration of oxidative stress and inflammation.

Hesperidin is a plant-derived bioflavonoid with promising antitumor efficacy, though the underlying mechanisms of action remain poorly elucidated. Thus, we evaluated the in vivo chemopreventive effect of hesperidin against diethylnitrosamine (DEN)-induced hepatocarcinogenesis. We demonstrated the modulatory effect of hesperidin on Nrf2/ARE/HO-1, PPARγ and TGF-ß1/Smad3 signaling. Hepatocarcinogenesis was initiated with DEN and promoted with carbon tetrachloride (CCl4). DEN/CCl4-induced rats were treated with 50 and 100 mg/kg hesperidin throughout the experiment. The results revealed that hesperidin significantly reduced circulating liver function marker enzymes, bilirubin, tumor markers and tumor necrosis factor alpha. Hesperidin prevented liver morphological damage, proliferating cell nuclear antigen (PCNA) expression and oxidative stress as evidenced by the reduced lipid peroxidation and enhanced antioxidant defenses. Liver NF-κB and TGF-ß1 expression, and Smad3 phosphorylation were significantly up-regulated in DEN/CCl4-induced rats. Hesperidin dramatically abolished NF-κB and TGF-ß1/Smad3 signaling as well as collagen deposition in the liver of DEN/CCl4-induced rats. In addition, hesperidin markedly up-regulated the expression of Nrf2, HO-1 and PPARγ in the liver of DEN/CCl4-induced rats. In conclusion, hesperidin can inhibit hepatocarcinogenesis by suppressing oxidative stress, inflammation, cell proliferation, TGF-ß1/Smad3 signaling and collagen deposition. These effects are suggested to be mediated by activating Nrf2/ARE/HO-1 and PPARγ pathways.

Protective effect of ellagic acid against cyclosporine A-induced histopathological, ultrastructural changes, oxidative stress, and cytogenotoxicity in albino rats.

Cyclosporine A (CsA) is an immunosuppressor agent, which is most frequently used in transplant surgeries and in the treatment of autoimmune diseases. This study was undertaken to investigate the protective effects of ellagic acid (EA) against CsA-induced testicular histopathology and ultrastructure changes, oxidative stress, and cytogenotoxicity in male albino rats. Rats were divided into six groups; the first group was used as a control, the second group received a subcutaneous injection of slightly alkaline solution, the third group received olive oil orally, the fourth group was injected subcutaneously with EA at a dose of 10 mg/kg b. wt./day, the fifth group was treated with CsA as oral solution at a dose of 15 mg/kg b. wt for 30 days, and the sixth group was treated with CsA simultaneously with EA. Treatment with EA simultaneously with CsA resulted in significant protection. The positive control animals taking CsA alone showed marked histopathological, ultrastructure, and genetic manifestations accompanied by an elevated content of lipid peroxidation and marked reduction of catalase (CAT), peroxidase (Px) activity, and glutathione concentration in the homogenate of testis tissues. The toxic side effects in testis and bone marrow tissues were greatly ablated with a significant reduction in lipid peroxidation level and elevation in CAT and Px activities and glutathione concentration when using EA. Thus, EA may be used in combination with CsA to improve the histopathological, oxidative stress, and cytogenotoxicity parameters of testicular toxicity induced by CsA due to its antioxidant effects.

Effect of diethylcarbamazine citrate and omega-3 fatty acids on trimellitic anhydride-induced rat skin allergy.

BACKGROUND: Diethylcarbamazine citrate (DEC) is the drug most widely used in the treatment of lymphatic filariasis. Omega-3 fatty acids (ω-3 FAs) are essential polyunsaturated fatty acids and commonly found in marine oils. Both have been applied in treatment of inflammatory diseases but anti-allergic effects should be investigated. OBJECTIVE: The present study was performed to test the effect of both DEC and ω -3 FAs on Trimellitic anhydride (TMA) - induced rat skin allergy. METHODS: In vivo experiment was executed in white albino rats using 100 and 600 mg/ Kg body weight of DEC and ω-3 FAs, respectively in treatment. Ear thickness of sensitized rats to TMA was monitored after challenge. Blood eosinophilia was determined using differential leukocyte count while the appearance of mast cells, eosinophils and collagen fibers in skin tissue were investigated using specific stains. Colorimetric assay of NO was performed in homogenized ears, while expression of inducible nitric oxide synthase (iNOS) was detected using immunohistochemistry. RESULTS: Ear thickness showed a significant (p < 0.05) reduction in both of DEC and ω-3 FAs treated groups. Blood eosinophilia and skin eosinophils were significantly (p < 0.001) decreased by DEC and ?-3 FAs, while the decrease of skin mast cells was only significant (p < 0.01) when ω-3 FAs applied. The expression of iNOS and intensity of stained collagen fibers were decreased obviously by ω-3 FAs but less by DEC treatment. Histopathological observations were more normal in ω-3 FAs than DEC treated groups. CONCLUSION: ω-3 FAs was more potent antiallergic substance against TMA-induced dermatitis than DEC.

Thymoquinone and curcumin attenuate gentamicin-induced renal oxidative stress, inflammation and apoptosis in rats.

The present study was aimed to investigate the possible protective effects of thymoquinone (TQ) and curcumin (Cur) on gentamicin (GM)-induced nephrotoxicity in rats. Rats were divided into four groups as follows: group 1 received normal saline and served as normal controls, group 2 received GM only, group 3 concurrently received GM and TQ and group 4 concurrently received GM and Cur. At day 21, rats were sacrificed and samples were collected for assaying serum tumor necrosis factor alpha (TNF-α), urea and creatinine levels, and renal lipid peroxidaion, glutathione (GSH) content as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. In addition, kidneys were collected for histopathological examination and immunohistochemical determination of the antiapoptotic protein, B-cell lymphoma 2 (Bcl-2). The biochemical results showed that GM-induced nephrotoxicity was associated with a significant increase in serum TNF-α, urea and creatinine as well as renal lipid peroxidation. On the other hand, renal GSH content and GPx and SOD activities were significantly declined. Concomitant administration of either TQ or Cur efficiently alleviated the altered biochemical and histopathological features. In conclusion, both TQ and Cur showed more or less similar marked renoprotective effect against GM-induced nephrotoxicity through their antioxidant, anti-inflammatory and anti-apoptotic efficacies.