Background/Objectives: Linezolid is an oxazolidinone antibiotic whose prolonged use is associated with peripheral neuropathy, hyperlactatemia, and metabolic acidosis. These adverse effects are primarily linked to the inhibition of mitochondrial protein synthesis, respiratory chain dysfunction, and oxidative stress. Given the central role of impaired energy metabolism and redox imbalance in drug-induced peripheral neuropathy, therapeutic strategies targeting mitochondrial function are of particular interest. Accordingly, this study aimed to comparatively evaluate the effects of adenosine triphosphate (ATP), coenzyme Q10 (CoQ10), pyridoxine, and thiamine pyrophosphate (TPP) on linezolid-induced peripheral neuropathic pain in rats. Methods: Sixty male albino Wistar rats were assigned to ten groups: healthy (HG); ATP-only (ATPG, 5 mg/kg, intraperitoneally); CoQ10-only (CQ10G, 10 mg/kg, orally); pyridoxine-only (PDXG, 50 mg/kg, orally); TPP-only (TPPG, 20 mg/kg, intraperitoneally); linezolid-only (LZDG, 125 mg/kg, orally); linezolid+ATP (ATLG); linezolid+CoQ10 (CQLG); linezolid+pyridoxine (PXLG); and linezolid+TPP (TPLG). Treatments were administered once daily for ATP, CoQ10, and TPP, and twice daily for linezolid and pyridoxine for 14 days. Oxidative stress indices (MDA, tGSH, SOD, CAT) were quantified in the sciatic nerve using ELISA. Serum lactate dehydrogenase (LDH) activity and blood lactate levels were determined to evaluate metabolic disturbances. Mechanical paw withdrawal thresholds were measured using the Randall–Selitto test both before and after treatment. Results: Linezolid significantly reduced paw withdrawal thresholds and induced oxidative stress, antioxidant depletion, increased LDH activity, and hyperlactatemia. Co-treatment with ATP and CoQ10 attenuated oxidative stress but did not significantly improve linezolid-induced reductions in nociceptive thresholds. In contrast, pyridoxine partially alleviated linezolid-induced neuropathic pain and improved biochemical parameters. Notably, TPP exerted the most robust protective effect, preserving nociceptive thresholds and effectively normalizing oxidative stress and metabolic indices. Conclusions: These findings identify TPP as a promising therapeutic strategy for mitigating linezolid-induced peripheral neuropathic pain by targeting mitochondrial energy metabolism and pyruvate–lactate homeostasis.

Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20 mg/kg, 2×1) was injected intramuscularly. Sertraline (30 mg/kg, 1×1) and tianeptine (5 mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.

Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to investigate and comparatively evaluate the protective effects of adenosine triphosphate (ATP) and taxifolin against atezolizumab-induced renal tissue injury in rats. Methods: Animals were divided into four groups: healthy (HG), atezolizumab (ATZ), ATP + atezolizumab (ATAZ), and taxifolin + atezolizumab (TXAZ). ATP (4 mg/kg, i.p.) and taxifolin (50 mg/kg, oral) were administered for six days, while atezolizumab (10 mg/kg, i.p.) was given on days 1 and 4. On day 7, renal tissues were collected for biochemical, histopathological, and double immunofluorescence analyses. Results: Atezolizumab significantly increased malondialdehyde (MDA) levels and decreased total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels, indicating enhanced oxidative stress and impaired antioxidant defense. These changes were accompanied by tubular degeneration and increased expression of apoptotic markers. Both ATP and taxifolin significantly ameliorated these alterations; however, ATP demonstrated a more pronounced protective effect. Conclusions: In conclusion, ATP and taxifolin attenuated the biochemical, histopathological, and immunofluorescence alterations associated with atezolizumab administration. ATP exhibited a more pronounced protective effect than taxifolin under the conditions of this experimental model. Nevertheless, further experimental studies are required to elucidate the mechanisms underlying these effects.

The toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity. Albino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction. ULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy. ULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is widely used in cancer therapy; however, hepatotoxicity limits its clinical use. This study investigated the protective effects of Liv-52, a polyherbal hepatoprotective formulation, against erlotinib-induced hepatotoxicity in rats and compared its efficacy with melatonin. The animals (n = 24, Wistar albino rats) were randomly categorized into four groups: healthy (HG), erlotinib (ERG), Liv-52 + erlotinib (LEG), and melatonin + erlotinib (MEG). Liv-52 (50 mg/kg/day, orally) and melatonin (10 mg/kg/day, orally) were administered once daily for two weeks. Erlotinib (10 mg/kg, orally) was given every other day to ERG, LEG, and MEG groups for two weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured. Hepatic malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed. Additionally, double immunofluorescence staining was performed to evaluate apoptotic (poly[ADP-ribose] polymerase-1 [PARP-1], apoptosis-inducing factor [AIF]), inflammatory (cyclooxygenase-2 [COX-2]), and anti-inflammatory (interleukin-10 [IL-10]) biomarkers in liver tissues. Histopathological examination was also conducted to assess structural alterations. Erlotinib significantly increased MDA, ALT, AST, and LDH while decreasing tGSH, SOD, and CAT (p < 0.001). Strong immunoreactivity for PARP-1, AIF, IL-10, and COX-2, as well as severe hydropic degeneration and necrosis, was observed in ERG (p < 0.05). Both Liv-52 and melatonin significantly ameliorated biochemical, histopathological, apoptotic, and inflammatory alterations (p < 0.05). Notably, Liv-52 demonstrated superior hepatoprotective efficacy compared to melatonin. These findings indicate that Liv-52 effectively attenuates erlotinib-induced hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, thereby preserving liver function and structural integrity.

Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine pyrophosphate (TPP) remain poorly defined. This study aimed to evaluate whether ATP and TPP mitigate metformin-induced renal injury through biochemical and histopathological assessments. Wistar rats were randomly divided into six groups: control, ATP, TPP, metformin, ATP + metformin, and TPP + metformin. Metformin (50 mg/kg, oral), ATP (4 mg/kg, intraperitoneal), or TPP (20 mg/kg, intraperitoneal) was administered daily for 10 days. Oxidative stress markers, inflammatory cytokines, renal histopathology, and serum creatinine, BUN, lactate, and LDH levels were evaluated. Metformin induced significant oxidative stress, inflammation, metabolic disturbance, and renal injury. ATP provided partial protection, whereas TPP markedly restored redox balance, reduced inflammation, and preserved renal histology. TPP confers superior protection against metformin-induced renal injury compared with ATP by modulating oxidative, inflammatory, and metabolic pathways, highlighting its therapeutic potential in preventing metformin-related nephrotoxicity.