Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

Arab, Hany H.; Salama, Samir A.; Abdelghany, Tamer M.; Omar, Hany A.; Arafa, El‐Shaimaa A.; Alrobaian, Majed; Maghrabi, Ibrahim A.

doi:10.1159/000480527

Cited by 46 publications

(42 citation statements)

References 45 publications

(92 reference statements)

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“…The selected doses for Camel milk are consistent with previous studies [13, 14, 16] and the dose of the reference antioxidant Quercetin is in line with previous literature [6]. …”

Section: Methodssupporting

confidence: 90%

“…These findings are in harmony with the reported CM suppression of MAPKs pathway in Adjuvant arthritis [13] and LPS-induced respiratory distress [47] along with abrogation of NF-κB signaling in wounds of diabetic rats [18]. Interestingly, blockade of MAPKs signaling, in particular, p38 and JNK pathways, has been shown to protect against acute renal failure, tubular cell apoptosis and histopathological damage in multiple renal injury models [5, 48].…”

Section: Discussionsupporting

confidence: 80%

“…CM possesses unique antioxidant features that are ascribed to its high content of vitamins C and E besides its high lactoferrin content, a bioactive protein with marked anti-oxidant and anti-inflammatory actions [12]. Several clinical and experimental studies have revealed the mitigating actions of CM against rheumatoid arthritis [13], inflammatory bowel disease [14], Diabetes mellitus [15], alcohol-induced hepatic injury [16], steatohepatitis [17] and wound healing [18]. More important, reports have indicated the efficacious role of CM in diabetes- [19], gentamicin- [20] and cisplatin-induced nephropathies [21].…”

Section: Introductionmentioning

confidence: 99%

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Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Arab

Salama

Maghrabi

2018

Cell Physiol Biochem

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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.

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“…The selected doses for Camel milk are consistent with previous studies [13, 14, 16] and the dose of the reference antioxidant Quercetin is in line with previous literature [6]. …”

Section: Methodssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Arab

Salama

Maghrabi

2018

Cell Physiol Biochem

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“…TNF‐α produced by LPL in the intestinal mucosa is an important inflammatory factor relevant to the pathogenesis of IBD, including the recruitment of inflammatory cells into the LP, the promotion of local inflammation of the intestinal mucosa, neutrophil/granulocyte aggregation and macrophage differentiation (Feagan et al ., ; Schiering et al ., ; Chamoun et al ., ; Lenzen et al ., ). A previous study result showed CM can reduce TNF‐α concentration in serum, thus decreasing the arthritis index and inflammatory cell migration into the intestinal tract, which is similar to the observations in the current study (Arab et al ., ). Furthermore, Treg cells producing IL‐10 influence homeostasis in the colon.…”

Section: Discussionmentioning

confidence: 97%

Camel milk regulates T‐cell proliferation to alleviate dextran sodium sulphate‐induced colitis in mice

Cui

Yue

et al. 2019

Int J of Food Sci Tech

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Summary The incidence of inflammatory bowel disease (IBD) is increasing in China. Current clinical methods of treatment for IBD are accompanied by side effects, and thus, the search for effective therapeutic drugs with minimal adverse effects is necessary. In the present study, the effects of camel milk (CM) on dextran sodium sulphate (DSS)‐induced acute and chronic colitis in a mouse model were investigated. The results showed CM effectively alleviated the injury induced by DSS to the colon mucosa and imbalance of immune cells in mice. However, treatment with CM significantly increased the body weight of mice and decreased the disease activity index (DAI), histopathological score, proliferation of Th17 cells and concentration of inflammatory cytokine IL‐17. The results from the present study indicate CM possesses intestinal protective effects.

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“…In camelids, glutathione peroxidase, which also belongs to the GSH biosynthesis pathway and is a potent anti-oxidant, has been identified as a seminal plasma fertility biomarker (Waheed et al, 2015). Furthermore, camel milk has been shown to boost glutathione and total anti-oxidant capacity in sera and exudates in animal studies (Arab et al, 2017). In a diabetic mouse model, the activities of GSH, alongside glucose insulin and ROS levels, were restored after camel whey protein treatment (Sayed et al, 2017).…”

mentioning

confidence: 99%

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Criscitiello

Kraev

Lange

2020

Molecular Immunology

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A B S T R A C TPeptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which posttranslationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies.

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Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

Cited by 46 publications

References 45 publications

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Camel milk regulates T‐cell proliferation to alleviate dextran sodium sulphate‐induced colitis in mice

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

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