Despite the continued global burden of tuberculosis and the essential role of isoniazid (INH) in first-line antituberculosis therapy, INH-induced neurotoxicity remains a major clinical challenge that compromises treatment adherence, and effective, well-characterized neuroprotective strategies are still lacking. This study investigated the neuroprotective effects of rosmarinic acid (RA) against INH-induced neurotoxicity, evaluating oxidative stress, inflammation, iron metabolism, energy homeostasis, mitochondrial dynamics, ferroptosis, and apoptosis using biochemical, molecular, and histopathological approaches. INH markedly increased malondialdehyde while reducing superoxide dismutase and glutathione, and increased TNF-α, IL-1β, and IL-6 while decreasing IL-10. INH also disturbed iron homeostasis (increased Fe²⁺), impaired energy metabolism (reduced ATP), and disrupted mitochondrial dynamics (increased Drp-1; decreased Mfn-2 and PGC-1α). NF-κB activation was accompanied by increased ACSL4 and decreased GPX4 and FTH1, reflecting ferroptosis, alongside increased Bax, Caspase-3, and Cytochrome c and reduced Bcl-2, indicating mitochondrial apoptosis. RA treatment suppressed oxidative stress, enhanced antioxidant defense, attenuated inflammation, restored iron and energy homeostasis, improved mitochondrial dynamics, and inhibited NF-κB activation, ferroptosis, and apoptosis. These findings demonstrate that RA exerts potent neuroprotective effects against INH-induced brain injury by simultaneously targeting oxidative stress, mitochondrial dysfunction, iron dyshomeostasis, neuroinflammation, ferroptosis, and apoptosis. To our knowledge, this is among the first studies to comprehensively address these interconnected pathways, including ferroptosis and iron dyshomeostasis, in INH-induced neurotoxicity. RA may thus represent a promising therapeutic candidate for preventing INH-induced neurotoxicity.
Merve Bolat, Tuba Karaarslan, S. Tekin et al.· Tissue & Cell· 0 citations
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.
Burak Batuhan Laçin, Furkan Aykurt, S. Tekin et al.· Erciyes Üniversitesi Veterin...· 0 citations
It is suggested that p-coumaric acid exerts neuroprotective effects against PbAc-induced brain injury by attenuating oxidative stress, neuroinflammation, and apoptosis while supporting neuronal plasticity.
Tuba Karaarslan, Merve Bolat, İsmail Bolat et al.· Biological Trace Element Res...· 0 citations
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