Anti-inflammatory and anti-oxidant activities of mesenchymal stem cells in chemically induced arthritic rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have been extensively used as cell-based treatments for decades due to their anti-inflammatory, immunomodulatory, and healing abilities. The intent of our study was to determine the efficacy of MSCs in alleviating rheumatoid arthritis (RA) induced by Complete Freund's adjuvant (CFA) and to investigate the anti-inflammatory and antioxidant characteristics of MSCs. METHODS AND RESULTS: Intrapedally injecting 0.1 ml of CFA directly into the footpad of the right hind paw daily for 2 days was used to induce RA. Arthritic rats received four doses of MSCs (1 × 106 cells/rat/dose) intravenously through the lateral tail vein. Our results showed that arthritic rats treated with MSCs exhibited reduced levels of paw edema. Furthermore, arthritic rats treated with MSCs exhibited a significant decrease in the levels of RF, CRP, IL-1ß, TNF-α, IL-17 and ADAMTS-5, along with a significant increase in the levels of IL-4 and TIMP-3. Additionally, MSCs significantly reduced the expression of TGF-ß. Both the glutathione (GSH) content and antioxidant activity of GST were enhanced by MSCs, while LPO levels were suppressed. CONCLUSION: These findings provide further evidence that MSCs are valuable in treating RA, possibly due to their anti-inflammatory and anti-oxidative properties. Thus, MSCs have potential as a more effective therapeutic strategy for treating RA.

A study on the therapeutic potential of graphene titanate nanocomposite for treating chemically induced arthritis in rats.

Nanotechnology holds substantial promise in the innovative therapies for rheumatoid arthritis (RA). The current study was designed to synthesize and characterize a new graphene titanate nanocomposite (GTNc) and explore its anti-arthritic, anti-inflammatory, and antioxidant potencies against Complete Freund's adjuvant (CFA)-induced arthritis in rats, as well as investigate the underlying molecular mechanisms. Our characterization methods included XRD, FT-IR, SEM, EDX, zeta potential, practical size, and XRF to characterize the novel GTNc. Our findings revealed that arthritic rats treated with GTNc exhibited lower levels of RF, CRP, IL-1ß, TNF-α, IL-17, and ADAMTS-5, and higher levels of IL-4 and TIMP-3. In arthritic rats, GTNc reduced LPO levels while increasing GSH content and GST antioxidant activity. Additionally, GTNc decreased the expression of the TGF-ß mRNA gene in arthritic rats. Histopathological investigation showed that GTNc reduced inflammatory cell infiltration, cartilage degradation, and bone destruction in joint injuries caused by CFA in the arthritic rats. Collectively, the anti-arthritic, anti-inflammatory, and antioxidant properties of GTNc appear promising for future arthritis treatments and bone disability research.

Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation.

Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin-dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2-related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1ß and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin's preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.

A Novel Hydroxyapatite/Vitamin B12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats.

The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B12 nanoformula in Complete Freund's adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1ß, TNF-α, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-ß mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freund's adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.

Protective Effects of Naringin-Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation.

Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin-dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.

Protective effects of Persea americana fruit and seed extracts against chemically induced liver cancer in rats by enhancing their antioxidant, anti-inflammatory, and apoptotic activities.

This study aims to explore the chemopreventive mechanisms of hydroethanolic extracts from avocado (Persea Americana) in diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced hepatocarcinogenesis. Chemical induction of hepatocarcinogenesis was induced by intraperitoneal injection of DEN at 150 mg/kg body weight (b.w.) twice a week for a fortnight, followed by oral administration of 2AAF at 20 mg/kg b.w. four times a week for 3 weeks. Rats administered DEN/2AAF were orally treated with hydroethanolic extracts of avocado fruits and seeds at a dose of 50 mg/kg b.w. every other day for 20 weeks. Moreover, rats administered DEN/2AAF and treated with avocado extracts revealed a marked decrease in liver enzyme activities, total bilirubin levels, and elevated liver tumor markers, but revealed an increase in total protein and albumin levels. The hepatocytes with hyperchromatic and bile duct cystadenoma observed in the liver of rats administered DEN/2AAF were reduced due to treatment with avocado extracts. Furthermore, the treatments prevented the elevation of lipid peroxidation levels and ameliorated the lowered glutathione peroxidase, glutathione-S-transferase, superoxide dismutase activities, and glutathione content in the liver tissues. Also, antigen Ki-67, cyclooxygenase-2, and nuclear factor kappa-B expression levels were decreased, but of the suppressor proteins p53 and BAX levels were increased in the liver of rats administered DEN/2AAF and treated with avocado extracts. In conclusion, the current results demonstrated that avocado extracts could abate hepatocarcinogenesis in rats administered DEN/2AAF through activation of antioxidant, anti-inflammatory, and apoptotic properties.

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls.