Radioprotective potential of whey protein against gamma irradiation-induced lingual damage.

Introduction: Ionizing radiation (IR) is effectively used in the treatment of oral malignancies; however, it might also significantly harm the surrounding tissues. Whey protein isolate (WP) is a protein derived from milk that exhibits a wide range of bioactivities. Therefore, the present research aimed to delineate the mitigating impact of WP against gamma irradiation-induced lingual damage. Methods: Rats were randomized into 5 groups: Control (saline, orally, 14 days), WP (WP; 0.5 g/kg b. w., orally, 14 days), IR (saline, orally, 14 days, exposed to 6 and 3 Gy on days 4 and 6, respectively), WP+IR (WP was given orally for 14 days before and after IR exposure; exposed to 6 and 3 Gy on days 4 and 6, respectively), and IR+WP (WP, orally, started 24 h after 1st IR exposure till the end of the experiment) groups. Samples were collected at two-time intervals (on the 7th and 14th days). Results and Discussion: Oxidative stress was stimulated upon IR exposure in tongue, indicated by boosted malondialdehyde (MDA) level, along with a decrease in the total antioxidant capacity (TAC) level, superoxide dismutase (SOD), and catalase (CAT) activities. Additionally, IR exposure depicted an increase of serum IgE, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, along with overexpression mRNA levels of nuclear factor kappa-B transcription factor/p65 (NF-κB/p65), and down-regulation of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase (HO-1) mRNA levels in tongue tissue. Moreover, IR triggered alterations in lingual histological architecture. The antioxidant and anti-inflammatory properties of WP mitigated oxidative damage, inflammation, and desquamation that were brought on following IR exposure. The protective administration of WP markedly decreases IR-induced lingual harm compared to the mitigation protocol. Our findings recommend WP supplements to the diets of cancer patients undergoing IR that might aid radioprotective effects.

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

The Combination of Tamarindus indica and Coenzyme Q10 can be a Potential Therapy Preference to Attenuate Cadmium-Induced Hepatorenal Injury.

Cadmium (Cd) is a hazardous environmental pollutant that menaces human and animal health and induces serious adverse effects in various organs, particularly the liver and kidneys. Thus, the current study was designed to look into the possible mechanisms behind the ameliorative activities of Tamarindus indica (TM) and coenzyme Q10 (CoQ) combined therapy toward Cd-inflicted tissue injury. Male Wistar rats were categorized into seven groups: Control (received saline only); TM (50 mg/kg); CoQ (40 mg/kg); Cd (2 mg/kg); (Cd + TM); (Cd + CoQ); and (Cd + TM + CoQ). All the treatments were employed once daily via oral gavage for 28 consecutive days. The results revealed that Cd exposure considerably induced liver and kidney damage, evidenced by enhancement of liver and kidney function tests. In addition, Cd intoxication could provoke oxidative stress evidenced by markedly decreased glutathione (GSH) content and catalase (CAT) activity alongside a substantial increase in malondialdehyde (MDA) concentrations in the hepatic and renal tissues. Besides, disrupted protein and lipid metabolism were noticed. Unambiguously, TM or CoQ supplementation alleviated Cd-induced hepatorenal damage, which is most likely attributed to their antioxidant and anti-inflammatory contents. Interestingly, when TM and CoQ were given in combination, a better restoration of Cd-induced liver and kidney damage was noticed than was during their individual treatments.

Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay.

Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.

Chronic oestrogen deficiency induced by ovariectomy may cause lung fibrosis through activation of the renin-angiotensin system in rats.

CONTEXT: Oestrogen deficiency is linked with pulmonary fibrosis. Additionally, it may lead to over-activation of the renin-angiotensin system (RAS), which worsens lung fibrosis. OBJECTIVE: The present study aims to investigate the role of RAS on lung fibrosis associated with oestrogen deficiency in ovariectomised rats. MATERIALS AND METHODS: Serum 17ß-oestradiol (E2), arterial blood gases, plasma angiotensin II levels, lung tissue hydroxyproline content, and transforming growth factor beta 1 (TGF-ß1) concentration, the mRNA expression of angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme (ACE1) were evaluated. Moreover, lung tissues were examined by histopathology and immunohistochemistry. RESULTS: Hydroxyproline content, TGF-ß1 concentration, plasma angiotensin II, the relative mRNA expression of ACE1, and AT1R is found to increase in ovariectomised rats. The mentioned changes can be largely rescued by administration of RAS blockers. CONCLUSION: Oestrogen deficiency activates RAS, which consequently increases the expression of pro-fibrotic factors and stimulates the fibrotic cascade causing lung fibrosis.

Adipose Tissue-Derived Mesenchymal Stem Cell Modulates the Immune Response of Allergic Rhinitis in a Rat Model.

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 µL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-ß (TGF-ß) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.

Effect of curcumin nanoparticles on the cisplatin-induced neurotoxicity in rat.

The present study is conducted to evaluate the neuroprotective effect of curcumin nanoparticles (CUR NP) against the neurotoxicity induced by cisplatin (CP) in rat. Rats were divided into control group that received saline solution, CP-treated rats that received a single i.p. injection of CP (12 mg/kg body wt), and CP-treated rats that received a single i.p injection of CP (12 mg/kg body wt) followed by a daily oral administration of CUR NP (50 mg/kg body wt) for 14 days. At the end of the experiment, the motor activity of rats was evaluated by open field test. The neurochemical and histopathological changes were investigated in the cerebral cortex. A significant decrease in motor activity was observed in CP-treated rats. This was associated with a significant increase in the cortical levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, caspase-3, and acetylcholinesterase activity. However, CP induced a significant decrease in reduced glutathione levels and Na+, K+-ATPase activity. In rats treated with CP and CUR NP, no significant changes were recorded in the parameters of the open field test as compared to control. In addition, treatment with CUR NP prevented all the neurochemical changes induced by CP except the increased value of nitric oxide. CUR NP also reduced the histopathological changes induced by CP. It is clear from the present data that CUR NP could ameliorate the neurotoxic effect induced by cisplatin.

Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway.

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes. RESULTS: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA. CONCLUSION: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

The glucagon-like peptide-1 receptor agonist Exendin-4, ameliorates contrast-induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia.

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury, particularly in diabetic patients. Previous studies have shown renoprotective effects of glucagon-like peptide-1 (GLP-1) signalling; however, its role in CIN remains unexplored. This study investigates the prophylactic effect of exendin-4, a GLP-1R agonist, against CIN in a rat model mimicking both healthy and diabetic conditions. Animals were randomly divided into 7 groups: a control sham group (n = 8), and 2 identical sets of 3 disease groups, one received exendin-4 before exposure to contrast medium (CM), while the other served as untreated control. The 3 disease groups represented diabetes (n = 8), CIN (n = 8), or diabetes and CIN combined (n = 8). Untreated groups showed deteriorating renal function as indicated by significantly higher levels of serum creatinine and blood urea nitrogen, malondialdehyde, and endothelin-1 and caspase-3 expression compared to the sham control group. This was accompanied by a significant decrease in tissue reserves of reduced glutathione, superoxide dismutase, nitrate and endothelin nitric oxide synthase as well as deteriorating renal histology. The CM-induced changes in diabetic rats indicate impaired renal function, oxidative stress, vascular dysfunction, and apoptosis, and were significance higher in intensity compared to non-diabetic rats. Pretreatment with exendin-4 ameliorated all the aforementioned CM-induced nephropathic effects independent of the glycemic state. To our knowledge, this is the first study describing the prophylactic renoprotective effects of exendin-4 against CIN. With the current pharmaceutical use of exendin-4 as a hypoglycaemic agent, the GLP-1R agonist becomes an interesting candidate for human clinical trials on CIN prevention.