Protective effects of microbial biosurfactants produced by Bacillus halotolerans and Candida parapsilosis on bleomycin-induced pulmonary fibrosis in mice: Impact of antioxidant, anti-inflammatory and anti-fibrotic properties via TGF-ß1/Smad-3 pathway and miRNA-326.

Idiopathic pulmonary fibrosis (IPF) is an irreversible disease which considered the most fatal pulmonary fibrosis. Pulmonary toxicity including IPF is the most severe adverse effect of bleomycin, the chemotherapeutic agent. Based on the fact that, exogenous surfactants could induce alveolar stabilization in many lung diseases, the aim of this study was to explore the effects of low cost biosurfactants, surfactin (SUR) and sophorolipids (SLs), against bleomycin-induced pulmonary fibrosis in mice due to their antioxidant, and anti-inflammatory properties. Surfactin and sophorolipids were produced by microbial conversion of frying oil and potato peel wastes using Bacillus halotolerans and Candida parapsilosis respectively. These biosurfactants were identified by FTIR, 1H NMR, and LC-MS/MS spectra. C57BL/6 mice were administered the produced biosurfactants daily at oral dose of 200 mg kg-1 one day after the first bleomycin dose (35 U/kg). We evaluated four study groups: Control, Bleomycin, Bleomycin+SUR, Bleomycin+SLs. After 30 days, lungs from each mouse were sampled for oxidative stress, ELISA, Western blot, histopathological, immunohistochemical analyses. Our results showed that the produced SUR and SLs reduced pulmonary oxidative stress and inflammatory response in the lungs of bleomycin induced mice as they suppressed SOD, CAT, and GST activities also reduced NF-κß, TNF-α, and CD68 levels. Furthermore, biosurfactants suppressed the expression of TGF-ß1, Smad-3, and p-JNK fibrotic signaling pathway in pulmonary tissues. Histologically, SUR and SLs protected against lung ECM deposition caused by bleomycin administration. Biosurfactants produced from microbial sources can inhibit the induced inflammatory and fibrotic responses in bleomycin-induced pulmonary fibrosis.

The mechanistic interplay between Nrf-2, NF-κB/MAPK, caspase-dependent apoptosis, and autophagy in the hepatoprotective effects of Sophorolipids produced by microbial conversion of banana peels using Saccharomyces cerevisiae against doxorubicin-induced hepatotoxicity in rats.

BACKGROUND: Doxorubicin (DOX) is a well-known chemotherapeutic agent which causes serious adverse effects due to multiple organ damage, including cardiotoxicity, nephrotoxicity, neurotoxicity, and hepatotoxicity. The mechanism of DOX-induced organ toxicity might be attributed to oxidative stress (OS) and, consequently, activation of inflammatory signaling pathways, apoptosis, and blockage of autophagy. Sophorolipids (SLs) as a glycolipid type of biosurfactants, are natural products that have unique properties and a wide range of applications attributed to their antioxidant and anti-inflammatory properties. AIMS: Production of low-cost SLs from Saccharomyces cerevisiae grown on banana peels and investigating their possible protective effects against DOX-induced hepatotoxicity. MAIN METHODS: The yeast was locally isolated and molecularly identified, then the yielded SLs were characterized by FTIR, 1H NMR and LC-MS/MS spectra. Posteriorly, thirty-two male Wistar rats were randomly divided into four groups; control (oral saline), SLs (200 mg/kg, p.o), DOX (10 mg/kg; i.p.), and SL + DOX (200 mg/kg p.o.,10 mg/kg; i.p., respectively). Liver function tests (LFTs), oxidative stress, inflammatory, apoptosis as well as autophagy markers were investigated. KEY FINDINGS: SLs were produced with a yield of 49.04% and treatment with SLs improved LFTs, enhanced Nrf2 and suppressed NF-κB, IL-6, IL-1ß, p38, caspase 3 and Bax/Bcl2 ratio in addition to promotion of autophagy when compared to DOX group. SIGNIFICANCE: Our results revealed a novel promising protective effect of SLs against DOX-induced hepatotoxicity in rats.

Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains.

BRIEF INTRODUCTION: Mucormycosis disease, which has recently expanded with the Covid 19 pandemic in many countries, endangers patients' lives, and treatment with common drugs is fraught with unfavorable side effects. AIM AND OBJECTIVES: This study deals with the economic production of sophorolipids (SLs) from different eight fungal isolates strains utilizing potato peels waste (PPW) and frying oil waste (FOW). Then investigate their effect against mucormycetes fungi. RESULTS: The screening of the isolates for SLs production revealed the highest yield (39 g/100 g substrate) with most efficiency was related to a yeast that have been identified genetically as Candida parapsilosis. Moreover, the characterizations studies of the produced SLs by FTIR, 1H NMR and LC-MS/MS proved the existence of both acidic and lactonic forms, while their surface activity was confirmed by the surface tension (ST) assessment. The SLs production was optimized utilizing Box-Behnken design resulting in the amelioration of yield by 30% (55.3 g/100 g substrate) and ST by 20.8% (38mN/m) with constant level of the critical micelle concentration (CMC) at 125 mg/L. The studies also revealed the high affinity toward soybean oil (E24 = 50%), in addition to maintaining the emulsions stability against broad range of pH (4-10) and temperature (10-100℃). Furthermore, the antifungal activity against Mucor racemosus, Rhizopus microsporus, and Syncephalastrum racemosum proved a high inhibition efficiency of the produced SLs. CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.

Sophorolipids produced by Yarrowia lipolytica grown on Moringa oleifera oil cake protect against acetic acid-induced colitis in rats: impact on TLR-4/p-JNK/NFκB-p65 pathway.

OBJECTIVES: Toll-like receptor-4 (TLR-4) activation plays a major role in triggering oxidative stress (OS) and inflammation implicated in the pathogenesis of ulcerative colitis (UC). Due to sophorolipids (SLs) antioxidant and anti-inflammatory properties, they are interestingly becoming more valued for their potential effectiveness in treating a variety of diseases. This study was designed to explore the effect of SLs produced by microbial conversion of Moringa oleifera oil cake using isolated yeast Yarrowia lipolytica against UC induced by acetic acid (AA) in rats. METHODS: The produced SLs were identified by FTIR, 1H NMR and LC-MS/MS spectra, and administered orally for 7 days (200 mg/kg/day) before AA (2 ml, 4% v/v) to induce UC intrarectally on day eight. Biochemically, the levels of TLR-4, c-Jun N-terminal kinase (JNK), nuclear factor kappa B-p65 (NFκB-p65), interleukin-1beta (IL-1ß), malondialdehyd, glutathione, Bax/Bcl2 ratio and the immunohistochemical evaluation of inducible nitric oxide synthase and caspase-3 were assayed. KEY FINDINGS: SLs significantly reduced OS, inflammatory and apoptotic markers in AA-treated rats, almost like the reference sulfasalazine. CONCLUSIONS: This study provided a novel impact for SLs produced by microbial conversion of M. oleifera oil cake against AA-induced UC in rats through hampering the TLR-4/p-JNK/NFκB-p65 signalling pathway.