Lemongrass Essential Oil Attenuates Perfluorooctane Sulfonate-Induced Jejunal Mucosal Injury in Rat: A Histological, Immunohistochemical, and Biochemical Study.

Perfluorooctane sulfonate (PFOS) has harmful impacts on various organs, including the intestine. Lemongrass essential oil (LGEO) has anti-inflammatory, anti-oxidant, antibacterial, and immunomodulatory effects. This study investigated the impact of PFOS on the mucosa of the jejunum of rats and evaluated LGEO's protective impact. Four groups of rats were created: control, LGEO (100 mg/kg/day), PFOS (5 mg/kg/day), and LGEO-PFOS group. The agents were given orally for 28 days. Oxidative stress parameters, pro-inflammatory cytokines, and caspase-3 were measured in jejunal homogenates. Rat jejunal sections were evaluated histologically (light and electron microscopic examination) and immunohistochemically [for tumor necrosis factor-α (TNF-α), Proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), and Bcl2]. PFOS significantly elevated oxidative stress, pro-inflammatory cytokines, caspase-3, and gene expression of nuclear factor kappa B (NF-kB) and inducible nitric oxide synthetase (iNOS). The disturbed architecture of jejunal villi and crypts was demonstrated. Immunohistochemically, a significant rise in TNF-α, PCNA, and COX2 and a significant decrease in Bcl2 expression were revealed compared to control group. Further ultrastructural alterations included dilated RER, mitochondria with destroyed cristae, vacuolated cytoplasm, and shrunken condensed nuclei of enterocytes. LGEO treatment significantly reduced these harmful effects. LGEO protected against PFOS-induced jejunal damage by reducing the oxidative, inflammatory, and apoptotic impacts.

Evening primrose oil attenuates oxidative stress, inflammation, fibrosis, apoptosis, and ultrastructural alterations induced by metanil yellow in the liver of rat: a histological, immunohistochemical, and biochemical study.

The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5 g/kg/day), Myl (200 mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities.

Moderating Gut Microbiome/Mitochondrial Axis in Oxazolone Induced Ulcerative Colitis: The Evolving Role of ß-Glucan and/or, Aldose Reductase Inhibitor, Fidarestat.

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). ß-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of ß-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, ß-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa ß (NF-kß), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kß, on the other hand, significantly decreased. Using ß-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness.

Adrenomedullin Mitigates Doxorubicin-Induced Nephrotoxicity in Rats: Role of Oxidative Stress, Inflammation, Apoptosis, and Pyroptosis.

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 µg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1ß, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM's antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity.