Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway.
TL;DR: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.
Abstract: Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.
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TL;DR: The results show that both caseins and whey proteins of camel milk possess bioactive peptides with significant radical-scavenging activities and thus herald a fascinating opportunity for their potential as nutraceuticals or therapeutic peptides for prevention and treatment of oxidative stress-associated diseases.
72 citations
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TL;DR: Interestingly, caffeic and ellagic acids attenuated the severity of arthritis with comparable efficacy to celecoxib, and these favorable findings may advocate the use of caffeo-ellagic acids as adjunct modalities for the management of RA to mitigate joint damage.
57 citations
TL;DR: The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K/Akt/eNOS pathway.
Abstract: Background/aims The clinical utility of 5-fluorouracil (5-FU) is limited by its nephrotoxicity. Camel milk (CM) has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. Methods Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA. The expression of MMP-2, MMP-9, NF-κBp65, p53, Bax and PCNA were detected by Immunohistochemistry. To gain an insight into the molecular signaling mechanisms, we determined the effect of CM on MAPKs, NF-κB and PI3K/Akt/eNOS pathways by Western blotting. Results CM lowered 5-FU-triggered increase of creatinine, BUN, Kim-1 and NGAL renal injury biomarkers and attenuated the histopathological aberrations. It suppressed oxidative stress and augmented renal antioxidant armory (GSH, SOD, GPx, TAC) with restoration of NOX-1, Nrf-2 and HO-1 levels. CM also suppressed renal inflammation as indicated by inhibition of MPO, TNF-α, IL-1β, IL-18 and MCP-1 proinflammatory mediators and downregulation of MMP-2 and MMP-9 expression with boosting of IL-10. Regarding MAPKs signaling, CM suppressed the phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 and inhibited NF-κB activation. For apoptosis, CM downregulated p53, Bax, CytC and caspase-3 proapoptotic signals with enhancement of Bcl-2 and PCNA. It also enhanced PI3K p110α, phospho-Akt and phospho-eNOS levels with augmentation of renal NO, favoring cell survival. Equally important, CM preconditioning enhanced 5-FU cytotoxicity in MCF-7, HepG-2, HCT-116 and PC-3 cells, thus, justifying their concomitant use. Conclusion The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K/Akt/eNOS pathway.
53 citations
TL;DR: The results of the present work highlight, for the first time, the ameliorating effects of troxerutin against gentamycin-induced AKI in rats that is potentially mediated via the modulation of p38 MAPK signaling as well as via antioxidant, anti-inflammatory and anti-apoptotic activities.
Abstract: Gentamycin is an aminoglycoside antibiotic that is widely employed for controlling Gram negative bacterial infections including that caused by the antibiotic-resistant Pseudomonas species. The clinical use of gentamycin is substantially limited by its side effects particularly acute kidney injury (AKI). The aim of the current study was to investigate the protective effect of the plant flavonoid troxerutin (150 mg kg-1 day-1 for 15 days) against gentamycin-induced AKI using Wistar rats as an experimental mammalian model. The results of the present work revealed that troxerutin significantly improved renal function as demonstrated by the increase in the glomerular filtration rate and the decrease in the levels of urinary albumin, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen (p < 0.001). In addition, troxerutin significantly attenuated gentamycin-induced renal tissue injury as indicated by the decreased protein expression of the renal tubular injury marker KIM-1, the attenuation of the renal histopathological changes, and the modulation of the oxidative stress markers as reflected by the decrease in the levels of lipid and protein oxidative modifications and the increase in the levels of reduced glutathione and total antioxidant capacity (p < 0.001). Furthermore, troxerutin down-regulated the levels of inflammatory cytokines (IL-10, TNF-α, and IL-6), attenuated apoptotic cell death, and enhanced the renal tissue regenerative capacity as demonstrated by the increase in the protein expression of the proliferating cell nuclear antigen, PCNA (p < 0.001). Collectively, the results of the current study highlight, for the first time, the ameliorating effects of troxerutin against gentamycin-induced AKI in rats that is potentially mediated via the modulation of p38 MAPK signaling as well as via antioxidant, anti-inflammatory and anti-apoptotic activities.
36 citations
TL;DR: The current findings demonstrate, for the first time, the renoprotective effects of CM in MTX-induced kidney injury via activation of PI3K/Akt/eNOS signaling and combating oxidative stress and apoptosis.
Abstract: Methotrexate (MTX) is a classical chemotherapeutic agent with nephrotoxicity as the most disturbing adverse effect. So far, its underlying molecular mechanisms, particularly PI3K/Akt/eNOS transduction, are inadequately explored. Several antioxidant modalities have been characterized to ameliorate MTX-induced renal injury. In this regard, Camel milk (CM) is a natural product with recognized antioxidant and anti-inflammatory features. Thus, the current study aimed to investigate the potential ameliorating effects of CM in MTX-induced kidney injury in rats. Renal tissues were studied in terms of renal injury markers, histopathology, oxidative stress, apoptosis and PI3K/Akt/eNOS signaling. CM was orally administered (10 ml kg-1) and the renal injury was induced by a single i.p. injection of MTX (20 mg kg-1). Interestingly, CM dose-dependently attenuated MTX-triggered increase of BUN and serum creatinine and renal Kim-1 expression and mitigated the renal histopathological changes. CM counteracted renal oxidative stress as manifested by lowering of lipid peroxides, restoration of NOX-1 levels and augmentation of the antioxidant defenses e.g., GSH, SOD, GPx and total antioxidant capacity. With respect to apoptosis, CM curbed the cleavage of PARP and caspase-3, downregulated p53, Bax and Cyt C proapoptotic signals and enhanced Bcl-2 and PCNA levels. In the same context, CM activated the prosurvival PI3K/Akt/eNOS pathway via enhancing PI3K p110, phospho-Akt and phospho-eNOS levels. Equally important, CM preconditioning did not interfere with MTX cytotoxicity in TK-10 or PC-3 cancer cells. Together, the current findings demonstrate, for the first time, the renoprotective effects of CM in MTX-induced kidney injury via activation of PI3K/Akt/eNOS signaling and combating oxidative stress and apoptosis.
36 citations
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TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.
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