Ali Çınar

Biological systems maintain functional integrity under environmental stress through tightly coordinated signaling networks, yet the mechanisms that preserve signal fidelity in the presence of stochastic oxidative and ionic fluctuations across taxa remain incompletely understood. Although redox regulation, coupling between reactive oxygen species (ROS) and Ca²⁺, and hormone-mediated feedback loops have been extensively characterized within individual kingdoms, a cross-kingdom framework linking these pathways through metabolite-mediated modulation is lacking. Here, a cross-kingdom compilation of evidence from plant, animal, and microbial systems is presented to examine how specific endogenous and microbe-derived metabolites and plant fructans modulate the fidelity of stress signaling networks. We propose a metabolite-guided signal fidelity hypothesis in which certain specialized metabolites act as molecular stabilizers in the response of organisms to stress. They buffer transient ROS bursts, limit variability in calcium signaling, and strengthen hormone-regulated feedback loops. Together, these functions preserve the signal-to-noise ratio of stress responses, independent of overt toxicity. These insights lay the groundwork for testable predictions and the development of translational strategies in agriculture, biotechnology, and medicine aimed at improving stress tolerance by stabilizing the flow of biological information.

Cadmium (Cd) is a highly toxic heavy metal that accumulates primarily in the kidneys, where it induces oxidative stress, inflammation, and cellular damage. Cd exposure is a major environmental and occupational concern due to its persistence and bioaccumulative nature. Morin, a natural flavonoid abundant in various fruits and medicinal plants, possesses potent antioxidant and anti-inflammatory properties. However, its potential protective efficacy against Cd-induced nephrotoxicity has not been fully elucidated. This study aimed to evaluate the protective effects of Morin against Cd-induced oxidative and inflammatory damage in rat kidney tissue and to assess its association with oxidative stress and inflammatory responses. Fifty adult male Sprague-Dawley rats were randomly divided into five groups: Control, Cd (6.5 mg/kg, i.p.), Morin100+Cd (100 mg/kg Morin + Cd), Morin200+Cd (200 mg/kg Morin + Cd), and Morin200 (200 mg/kg Morin alone). Cadmium was administered intraperitoneally for 5 consecutive days, while Morin was given intragastrically one hour before Cd injection. Cadmium exposure significantly elevated malondialdehyde (MDA) levels and proinflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) while reducing the activities of antioxidant enzymes (SOD, CAT, GPx, GSH) and anti-inflammatory cytokines (IL-10, IL-4). Morin treatment, particularly at 200 mg/kg, markedly ameliorated these alterations by suppressing oxidative stress, restoring antioxidant enzyme activities, and modulating cytokine balance. These findings indicate that Morin exerts a strong nephroprotective effect against Cd-induced renal toxicity through attenuation of oxidative stress and inflammation, possibly associated with its antioxidant and anti-inflammatory properties. Therefore, Morin may represent a promising natural therapeutic candidate for the prevention of heavy metal-induced renal injury.

This study investigated the protective effects of zingerone (ZIN) against thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats (n = 10 per group). HE was induced by TAA (200 mg/kg, intraperitoneally (i.p.)) on days 1 and 3, and rats were treated with ZIN (25 or 50 mg/kg/day, intragastric gavage (i.g.)) for 14 days. Serum biochemistry, oxidative stress, inflammatory markers, ER stress-related proteins, apoptosis indicators, histopathology, and behavioral outcomes were evaluated TAA administration markedly increased whole-blood ammonia concentrations together with serum activities of the hepatic injury biomarkers ALT, AST, ALP, GGT, and LDH compared with the Control group, while ZIN treatment significantly improved these parameters. ZIN reduced malondialdehyde (MDA) levels and restored antioxidant defenses (SOD and GSH) in both liver and brain tissues. Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were elevated after TAA exposure, whereas IL-10 was reduced; ZIN dose-dependently reversed these changes. In addition, TAA increased ER stress markers (GRP78, CHOP, ATF6, XBP1, IRE1, and PERK) and apoptosis-related Bax and caspase-3 expression, which were significantly suppressed by ZIN. In brain tissue, ZIN preserved BDNF expression and reduced GFAP immunoreactivity. Behavioral impairments, including anxiety-like behavior and locomotor deficits, were significantly improved at 50 mg/kg. Overall, ZIN exhibited dose-dependent hepatoprotective and neuroprotective effects in TAA-induced hepatic encephalopathy, as evidenced by attenuation of oxidative stress, inflammation, ER stress, and apoptosis. This study provides an integrated evaluation of ZIN in hepatic encephalopathy, extending prior findings in other hepatotoxicity models, including CCl₄ and cadmium-induced injury, as well as related phytochemical studies in HE.

Lead is a highly toxic heavy metal and an environmental pollutant. Lead exposure causes damage and dysfunctions in organs. In tissues exposed to lead, ROS increase, resulting in oxidative stress, inflammation and apoptosis. In this study, we aimed to investigate the protective effects of Borago officinalis (BO) against lead, whose toxic effects are well-established. In this study, 40 Sprague-Dawley rats were used. The rats were randomly divided into 5 groups. The groups were determined as control, BO100, Pb (20 mg/kg), Pb+BO50 and Pb+BO100. After the experimental procedures were completed, the tissues were transported in cold chain and stored in -80 deep freezer until the experiments were performed. Keap-1 level was determined in spleen tissue using Western blot method. At the same time, IL-1β, IL-10, NF-ĸB, Bax, Bcl-2, Caspase-3 levels were determined by RT-PCR method. BO administration stimulated Keap-1 level in relation to oxidative stress. While BO suppressed IL-1β and NF-ĸB levels, it stimulated IL-10 level, which are anti-inflammatory markers. BO also suppressed Bax and Kaspas-3 levels, while significantly stimulating Bcl-2 level. With these effects, it was observed that BO had anti-oxidant, anti-inflammatory, anti-apoptotic effects in the spleen tissue of rats treated with lead acetate.

This study examined the antioxidant, anti-inflammatory, and neuroprotective effects of melatonin (MEL) against acrylamide (ACR)-induced neurotoxicity in Sprague-Dawley rats. The experimental groups included control, ACR, MEL10+ACR, MEL20+ACR, and MEL20. MEL at doses of 10 and 20 mg/kg, and ACR at 50 mg/kg, were administered intraperitoneally for 14 days. On the 15th day, locomotor activity was assessed, and brain tissues were analyzed biochemically, molecularly, and histopathologically. ACR exposure decreased locomotor activity, increased malondialdehyde (MDA) and reduced glutathione (GSH) levels, indicating oxidative stress, and decreased antioxidant enzyme activities (SOD, GPx, CAT). High-dose MEL (MEL20+ACR) effectively reduced lipid peroxidation and restored antioxidant enzyme activities. MEL treatment also suppressed proinflammatory cytokines (TNF-α, IL-1β, IL-6) and neuronal nitric oxide synthase (nNOS), demonstrating anti-inflammatory effects. Furthermore, MEL mitigated ACR-induced neurotoxicity by reducing acetylcholinesterase (AChE) and monoamine oxidase (MAO) levels. ER stress markers (GRP78, ATF4, ATF6, sXBP1, CHOP) and apoptotic markers (Bax, Caspase-3) were elevated following ACR exposure but were suppressed by MEL. Additionally, MEL reduced ACR-induced increases in 8-hydroxy-2-deoxyguanosine (8-OHdG) and glial fibrillary acidic protein (GFAP), markers of DNA damage and astrocyte activation, respectively. These findings underscore the potential of MEL to counteract ACR-induced neurotoxicity through its comprehensive antioxidant, anti-inflammatory, and neuroprotective actions.

In this study, it was aimed to investigate the protective effects of Naringin on nephrotoxicity by Cyclophosphamide (CYP)-induced rats. In our study, forty male adult Sprague Dawley rat weighing approximately 200-250 g were used and 5 gropus formed. Measurement of hematologic and biochemical parameters were done in the rat mode on the Abocus Junior Vet 5 hemogram and on Modular PP autoanalyzer instruments. In the CYP groups, Neutrophil (%) and monocyte (%) increase despite red blood cell count, white blood cell count, hematocrit value, thrombocyte count and lymphocyte (%) decrease (P<0.05). While there were a decrease in potasium and sodium levels (P<0.05), but no decrease in other parameters such as phosphorus, magnesium, chlorine and calcium. Altough glucose, creatinine and uric acid levels from renal function tests were statistically significantly increased at (P<0.05), the increase in urea, BUN and lactate dehydrogenase (LDH) values were not significant. In the histopathological exemination; It was determined that severly hydropic degeneration and coagulation necrosis in tubule ephitelia, dilatation in Bowman capsule, hyperemia in interstitial vein and glomerulus of kidney tissue by the effects of CYP. These damages in the kidney were found to be reduced as dose-dependent due to cytoprotective effects of Naringin. It was determined that different doses of Naringin suppress nephrotoxicity and the negative effect of CYP.

This study was carried out to determine vit. E, Se, vit. A, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and ubiquinone-10 (CoQ10) levels and histopathological changes in sheep with white muscle disease (WMD). A total of 30 sheep were used; 20 sheep with WMD were brought to our clinic for diagnosis and treatment at various times, and 10 healthy sheep were in the control group. The Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 values of the healthy and WMD sheep were as follows: 0.917 ± 0.037, 0.790 ± 0.067; 1.190 ± 0.011, 1.090 ± 0.021; 5.400 ± 0.275, 5.200 ± 0.173; 1.602 ± 0.264, 2.636 ± 0.576; 0.656 ± 0.197, 1.485 ± 0.271; and 0.280 ± 0.044, 1.753 ± 0.551 respectively (p < 0.05). According to histopathological and immunohistochemical findings in the WMD group, hyaline degeneration, Zenker’s necrosis, and dystrophic calcification were observed in the muscle fibers. Immunohistochemically, 8-OHdG staining of the heart tissue determined a severe 8-OHdG expression in the WMD group. The findings of this study suggest that MDA, 8-OHdG, and CoQ10 values could be used as diagnostic and prognostic biomarkers in sheep affected with WMD.