Özge Kandemir

OBJECTIVE: The aim of this study is to investigate the protective effects of rutin against lower-extremity ischemia-reperfusion (IR)-induced skeletal muscle injury in rats, focusing on oxidative stress, inflammation, endoplasmic reticulum (ER) stress, and apoptosis, considering rutin’s well-known strong antioxidant and anti-inflammatory properties.MATERIAL AND METHODS: Twenty-eight male Wistar rats were randomly divided into four groups: control, rutin, IR, and IR+rutin. Hind limb ischemia was induced by applying a tourniquet to the upper limb for 2 hours, followed by 2 hours of reperfusion. Rutin was administered orally at a dose of 100 mg/kg prior to ischemia. Skeletal muscle tissue samples were analyzed for oxidative stress markers (MDA, SOD, CAT, GPx, GSH) using spectrophotometric biochemical assays; inflammatory mediators (NF-κB, IL-1β mRNA), endoplasmic reticulum stress markers (PERK, ATF6, IRE1α mRNA), and apoptotic markers (Bax, Bcl-2, caspase-3) were evaluated by RT-PCR. Histopathological changes were examined in sections prepared from the gastrocnemius muscle using H&E staining.RESULTS: Ischemia-reperfusion led to a significant increase in MDA levels and in the mRNA expression of NF-κB, IL-1β, PERK, ATF6, IRE1α, Bax, and caspase-3, accompanied by a reduction in antioxidant enzyme activities (SOD, CAT, GPx) and GSH content. Rutin exhibited protective activity against IR-induced muscle damage by strengthening endogenous antioxidant defenses and suppressing stress-related signaling pathways. Consistently, histopathological evaluation demonstrated that rutin mitigated muscle fiber disorganization, vascular congestion, and inflammatory cell infiltration.CONCLUSIONS: Oral rutin administration exerts strong protective effects against skeletal muscle IR injury by modulating oxidative stress, inflammatory responses, ER stress, and apoptosis. These findings highlight rutin as a promising pharmacological candidate for protecting skeletal muscle integrity in post-ischemic conditions.

The aim of protective role of folic acid (FA) against indomethacin (IND)-induced hepatotoxicity in rats. In particular, the study focused on the capacity of FA to mitigate oxidative stress-related hepatic injury. The results demonstrated that FA treatment markedly attenuated liver damage when compared with the untreated control group. Antioxidant defense system revealed that IND administration led to significant reduction in catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities, together with decreased glutathione (GSH) levels, whereas these parameters were improved following FA treatment. Moreover, FA administration lowered malondialdehyde (MDA) concentrations, an important indicator of lipid peroxidation. FA also exhibited notable anti-inflammatory effects by suppressing proinflammatory mediators, particularly through downregulation of interleukin-1 beta (IL-1β) expression and inhibition of nuclear factor kappa-B (NF- κB) activation. In addition, FA reduced the IND-induced elevation of the proapoptotic proteins Bcl-2-associated X protein (Bax) and cysteine-aspartic protease-3 (Caspase-3), while enhancing the transcriptional activity of the antiapoptotic gene B-cell lymphoma-2 (Bcl-2). Biochemical analyses further indicated that FA alleviated hepatic tissue injury by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels elevated by IND exposure. With respect to oxidative stress-associated signaling pathways, the IND-treated group exhibited decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels alongside increased Keap1 expression. In contrast, IND+FA group showed a statistically significant increase in Nrf2 and HO-1 levels and a reduction in Keap1 expression relative to the IND group. Overall, these findings suggest that FA exerts a protective effect against IND-induced liver toxicity and may alleviate hepatic damage through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Amoxicillin-clavulanic acid (AMC) is frequently implicated in drug-induced hepatic damage during antimicrobial therapy; however, the molecular mechanisms driving this adverse event remain poorly understood. Carvacrol (CRV), a monoterpenic phenol, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to investigate whether CRV exerts a hepatoprotective effect against AMC-induced liver injury. Male Wistar albino rats (n=28) were allocated into four groups: control, AMC (30 mg/kg), CRV (50 mg/kg), and AMC+CRV, administered via oral gavage daily for seven days. Hepatic damage was evaluated by assessing liver function markers, oxidative stress parameters, inflammatory pathways, autophagic markers, and histopathological alterations. AMC administration induced acute hepatic injury, significantly elevating serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. AMC also increased hepatic malondialdehyde (MDA) content, upregulated pro-apoptotic proteins (Caspase-3 and Bax), and elevated inflammatory markers [nuclear factor kappa B (NF-κB), interleukin-17A (IL-17A), and interleukin-1β (IL-1β)], alongside autophagic markers [Beclin-1 and Light chain 3A (LC3A)]. Conversely, AMC suppressed glutathione levels, reduced superoxide dismutase, catalase, and glutathione peroxidase activities, and downregulated the anti-apoptotic protein B-cell lymphoma-2 (BCL-2). Co-administration of CRV with AMC significantly attenuated AST, ALT, MDA, NF-κB, IL-17A, IL-1β, Caspase-3, Bax, Beclin-1, and LC3A levels, while successfully restoring antioxidant defenses and BCL-2 expression. Furthermore, CRV markedly ameliorated AMC-induced histopathological tissue damage. Collectively, these findings suggest that CRV exerts a protective effect against AMC-induced hepatotoxicity, associated with the attenuation of oxidative stress, apoptosis, autophagy, and inflammation.

Docetaxel (DTX), a cornerstone chemotherapeutic agent, has its clinical utility significantly limited by dose‐dependent nephrotoxicity. This study investigated the multi‐pathway renoprotective mechanisms of betanin (BTN), a natural antioxidant derived from beetroot, against DTX‐induced kidney injury. Male Wistar rats received DTX (30 mg/kg, i.p., single dose) with or without BTN (100 mg/kg/day, p.o.) for 7 days. DTX induced severe renal dysfunction with elevated serum urea and creatinine, and significant oxidative stress characterized by increased MDA and decreased GSH, GPx, SOD, and CAT. Molecular analysis demonstrated widespread upregulation of pro‐inflammatory (NF‐κB, TNF‐α, IL‐1β), endoplasmic reticulum stress (PERK, ATF6), pro‐apoptotic (Caspase‐3, Bax, Apaf‐1), and pro‐ferroptotic (PTGS2, TfR1) mediators, with concurrent downregulation of protective Bcl‐2 and GPx4. Histopathological examination revealed extensive tubular injury, while immunohistochemical analysis showed markedly increased kidney injury marker KIM‐1 and decreased aquaporin‐1 expression. Remarkably, BTN co‐administration significantly attenuated all biochemical, molecular, and structural derangements, restored tissue architecture, and normalized KIM‐1 and AQP‐1 expression. In conclusion, betanin provides robust, multi‐pathway renoprotection against docetaxel‐induced nephrotoxicity by concurrently targeting oxidative stress, inflammation, ER stress, apoptosis, and ferroptosis.

This study evaluated polydatin's protective effects against methotrexate (MTX)-induced hepatotoxicity in rats. Thirty-five Wistar albino rats were divided into (n=7): Control, Polydatin-only (100 mg/kg), MTX-only (20 mg/kg), MTX + Polydatin (50 mg/kg), and MTX + Polydatin (100 mg/kg). Treatments lasted 7 days. MTX administration significantly increased serum AST/ALT levels, hepatic malondialdehyde (MDA), and pro-inflammatory/apoptotic markers (NF-κB, TNF-α, Bax, Caspase-3 mRNA), while decreasing anti-apoptotic Bcl-2 and tissue-repair signals (Wnt3 mRNA). Co-treatment with polydatin dose-dependently reversed these effects: the 100 mg/kg dose notably normalized AST/ALT and MDA levels more effectively than 50 mg/kg (p

Oxaliplatin (OXI), a platinum‐based chemotherapeutic agent commonly used in colorectal Cancer treatment, has been linked to significant nephrotoxicity involving apoptosis, endoplasmic reticulum (ER) stress, inflammation, oxidative stress, and autophagy. This study investigated the potential mechanisms involved in kidney damage caused by OXI and explored the renoprotective effects of lycopene (LP) in renal tissues of rats. Biochemical analyses revealed that OXI administration led to elevated serum urea and creatinine levels, increased lipid peroxidation (MDA), and decreased antioxidant defense (SOD, CAT, GPx, GSH), accompanied by suppression of the Nrf‐2/HO‐1 pathway. Inflammatory markers such as NF‐κB, IL‐1β, COX‐2, TNF‐α, and iNOS were significantly upregulated, along with ER stress‐related genes (GRP78, ATF6), apoptotic markers (p53, Bax, Bcl‐2), and key mediators of autophagy (Beclin‐1, JNK). Additionally, Western blot and immunohistochemistry results indicated increased expression of AKT, mTOR, and PI3K proteins in the OXI group, suggesting altered survival signaling. LP treatment ameliorated these pathological alterations by restoring antioxidant enzyme activities, downregulating proinflammatory and proapoptotic signals, mitigating ER stress and autophagy activation, and reducing PI3K/AKT/mTOR protein expression. These findings demonstrate that LP exerts a renoprotective effect against OXI‐induced kidney injury through multi‐targeted molecular mechanisms, including modulation of inflammation, oxidative stress, autophagy, apoptosis, and survival signaling pathways.

This study aimed to evaluate whether polydatin (Poly) could eliminate the harmful effects of vancomycin (VCM) on the lungs of rats. Rats were administered VCM (200 mg/kg) and Poly (50 mg/kg), both separately and in combination, for a duration of 7 days. Following this, various methods were utilized to analyze proteins and pathological changes in lung tissue related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and ferroptosis. It was found that Poly application significantly enhanced antioxidant enzyme activities and nonenzymatic antioxidants while decreasing VCM‐induced lipid peroxidation. The study showed that VCM elevated the expression of inflammatory cytokines as well as Janus kinase 2 (JAK‐2) and signal transducer and activator of transcription 3 (STAT‐3), whereas Poly treatment inhibited these genes. Furthermore, VCM was found to induce apoptotic markers, but Poly offered protection to lung tissue against the harmful effects of VCM by demonstrating an antiapoptotic effect. Additionally, the increased expression of prostaglandin endoperoxide synthase 2 (PTGS2) and transferrin receptor 1 (TFR1), along with the decreased expression of glutathione peroxidase 4 (GPX4) in lung tissue induced by VCM, showed improvement following Poly administration. VCM was observed to increase, while Poly decreased the expression of endoplasmic reticulum stress markers. Overall, the findings of this study suggest that Poly has therapeutic potential in combating VCM‐induced lung toxicity.