Antioxidant efficacy of Cotoneaster nummularius in phenylhydrazine-induced hyperbilirubinemia: A rat model study

BACKGROUNDAceclofenac (ACF), a widely used nonsteroidal anti-inflammatory drug, has been associated with a number of severe cases of clinical hepatotoxicity. Terminalia bellirica, an evergreen tree, is known to have several ethnomedicinal uses including antioxidant and hepatoprotective effects. Hence T. bellirica fruit extracts and its phytoconstituent ellagic acid (EA) are expected to provide protection against oxidative stress and liver damage produced by long-term use of ACF. AIMTo evaluate the antioxidant and hepatoprotective activities of T. bellirica fruit extracts and EA against ACF-induced toxicity in albino Wistar rats.METHODSThe in vitro antioxidant activities of T. bellirica fruit ethyl acetate and aqueous extracts were measured by metal ion chelation and nitric oxide radical scavenging assays. The in vivo antioxidant and hepatoprotective effects of T. bellirica extracts (200 mg/kg) and EA (40 mg/kg) in ACF-induced hepatotoxic rats were assessed in serum and liver tissue after oral administration for 21 d. Silymarin (40 mg/kg) was used as a standard control. Oxidative stress markers in the blood (ferric reducing ability of plasma and lipid peroxidation inhibition) and liver tissues (superoxide dismutase, catalase and malondialdehyde) were analyzed using standard protocols. Liver function markers such as alkaline phosphatase, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, lactate dehydrogenase, γ-glutamyl transferase, creatinine, total protein, and uric acid were evaluated in rat serum.RESULTSThe T. bellirica fruit ethyl acetate extract exhibited superior metal ion chelating and nitric oxide radical scavenging abilities during in vitro antioxidant assays as compared to aqueous extracts. Oral administration of ACF in rats (15 mg/kg) for 21 d produced oxidative stress and adversely affected liver function suggesting liver injury. Treatment with extracts (ethyl acetate and aqueous), EA and silymarin accounted for a significant reduction in the adverse effects of ACF on oxidative stress and liver function markers in serum and hepatic tissue in rats. Histopathological evaluation of the liver indicated that the extracts and EA significantly decreased the degree of liver damage. The in vivo efficacy of EA was higher than T. bellirica fruit extracts. Of these extracts, ethyl acetate extract revealed comparatively better antioxidant and hepatoprotective activity.CONCLUSIONEllagic acid and T. bellirica fruit extracts exhibited considerable hepatoprotective and antioxidant activities in long-term ACF-treated rats.

Bak deficiency inhibits liver carcinogenesis: A causal link between apoptosis and carcinogenesis

BackgroundIn malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).MethodsForty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.ResultsExposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.ConclusionIrrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.

Oxidative stress is proposed in the literature as an important player in the development of CHF and correlates with left ventricle (LV) dysfunction and hypertrophy in the failing heart. In this study, we aimed to verify if the serum oxidative stress markers differ in chronic heart failure (CHF) patients' groups depending on the LV geometry and function. Patients were stratified into two groups according to left ventricular ejection fraction (LVEF) values: HFrEF (<40% (n = 27)) and HFpEF (≥40% (n = 33)). Additionally, patients were stratified into four groups according to LV geometry: NG-normal left ventricle geometry (n = 7), CR-concentric remodeling (n = 14), cLVH-concentric LV hypertrophy (n = 16), and eLVF-eccentric LV hypertrophy (n = 23). We measured protein (protein carbonyl (PC), nitrotyrosine (NT-Tyr), dityrosine), lipid (malondialdehyde (MDA), oxidizes (HDL) oxidation and antioxidant (catalase activity, total plasma antioxidant capacity (TAC) markers in serum. Transthoracic echocardiogram analysis and lipidogram were also performed. We found that oxidative (NT-Tyr, dityrosine, PC, MDA, oxHDL) and antioxidative (TAC, catalase) stress marker levels did not differ between the groups according to LVEF or LV geometry. NT-Tyr correlated with PC (rs = 0.482, p = 0.000098), and oxHDL (rs = 0.278, p = 0.0314). MDA correlated with total (rs = 0.337, p = 0.008), LDL (rs = 0.295, p = 0.022) and non-HDL (rs = 0.301, p = 0.019) cholesterol. NT-Tyr negatively correlated with HDL cholesterol (rs = -0.285, p = 0.027). LV parameters did not correlate with oxidative/antioxidative stress markers. Significant negative correlations were found between the end-diastolic volume of the LV and the end-systolic volume of the LV and HDL-cholesterol (rs = -0.935, p < 0.0001; rs = -0.906, p < 0.0001, respectively). Significant positive correlations between both the thickness of the interventricular septum and the thickness of the LV wall and the levels of triacylglycerol in serum (rs = 0.346, p = 0.007; rs = 0.329, p = 0.010, respectively) were found. In conclusions, we did not find a difference in serum concentrations of both oxidant (NT-Tyr, PC, MDA) and antioxidant (TAC and catalase) concentrations in CHF patients' groups according to LV function and geometry was found. The geometry of the LV could be related to lipid metabolism in CHF patients, and no correlation between oxidative/antioxidant and LV markers in CHF patients was found.

Angiotensin II (Ang II), the primary peptide of the Renin Angiotensin System (RAS), can induce the production of reactive oxygen species (ROS) and affect mitochondrial energetics, predisposing to age‐related disorders. Angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) can attenuate ROS production, improve mitochondrial function and increase survival in aging rodents, however, the effects of losartan, an ARB, on age‐associated oxidative damage in rhesus monkeys have not been yet explored. We have previously shown that mitochondrial DNA (mtDNA) damage, depletion of mtDNA molecules and oxidative stress increase in liver and blood leukocytes of middle‐age and old rhesus monkeys. We hypothesize that losartan treatment prevents oxidative damage in liver and blood leukocytes from rhesus monkeys. To test our hypothesis we examined the effects of losartan on mtDNA, nuclear DNA (nDNA) and protein damage, mtDNA abundance in whole blood and liver and metabolic parameters in losartan‐treated and age‐matched untreated middle‐age rhesus monkeys. Middle‐age rhesus monkeys (8–19 years of age) were treated with losartan (30mg/day) for 12 months and samples were obtained at baseline, 3, 6, and 12 months after treatment. Young (3–6 years of age) untreated monkeys were also analyzed as a control for the effects of aging. Fasting insulin and fasting glucose were measured in the serum and mitochondrial DNA (mtDNA) damage and abundance, and nuclear DNA (nDNA) damage were assessed by quantitative PCR. Protein carbonylations were measured in peripheral blood mononuclear cells (PBMCs) and liver of rhesus monkeys using the FTC Fluorometric assay. Interestingly, we found that losartan significantly decreased fasting blood glucose levels in healthy middle‐age monkeys after 12 months of treatment when compared to age‐matched untreated animals. No effects were observed on systolic/diastolic blood pressure, fasting insulin, cholesterol, tryglycerides and glycated hemoglobin levels. In whole blood samples, middle‐age monkeys exhibit significant increased levels of nDNA lesions compared to young animals, and treatment with losartan decreased nDNA damage to levels similar to young animals. Moreover, we found a significant decrease in the levels of carbonylated proteins in PBMCs from middle‐age monkeys treated with losartan compared to untreated monkeys, indicative of lower levels of oxidative stress. No significant differences were observed in the levels of mtDNA copies between the groups. In liver, middle‐age monkeys exhibited decreased levels of mtDNA molecules and losartan had no effect on preventing the loss of mtDNA copies. In contrast to PBMCs, no significant differences were observed in nDNA lesions and protein carbonylations between groups. Surprisingly, losartan significantly increased the levels of mtDNA damage as compared to young animals. Collectively, our results suggest that losartan precludes nDNA (but not mtDNA) and protein oxidative damage in PBMCs (but not in liver) and improves glucose levels in healthy middle‐age rhesus monkeys.Support or Funding InformationP40RR003640R25 GM061838U54 MD007600This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Rheumatoid arthritis (RA) as a chronic inflammatory disease is associated with oxidative stress. Drugs targeting tumor necrosis factor-alpha (TNF-α) ameliorate inflammation and symptoms of RA in most patients. Whether markers of oxidative stress can be used for monitoring of treatment effects is unknown. The aim of our study was to analyze the effects of anti-TNF-α treatment on oxidative stress in plasma and saliva of patients with RA. Samples were collected from 26 patients with RA at baseline as well as 3 and 6 months after starting the anti-TNF-α treatment. Thiobarbituric acid-reacting substances (TBARS), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and fructosamine were quantified using spectrophotometry and spectrofluorometry in plasma. TBARS were measured also in saliva. The disease activity score (DAS28) was used to assess the clinical status of patients. No significant dynamic changes were found except plasma TBARS that decreased continuously. At 6 months after starting the treatment, plasma TBARS were lower by 39% in comparison to baseline (p = 0.006). Salivary concentrations of TBARS did not reflect the dynamics in plasma. Although a trend was observed (r = 0.33), a significant correlation between plasma TBARS and DAS28 was not found. Our results indicate that anti-TNF-α treatment decreases plasma TBARS as a marker of lipid peroxidation. However, the lack of a significant correlation with DAS28 suggests that it cannot be used for monitoring of treatment. Other markers of oxidative stress and antioxidant capacity with lower biological variability should be tested in future studies.

Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P < 0.001), and higher in pseudo-exfoliative glaucoma vs primary angle closed glaucoma (effect size = 12.2; 95%CI 8.96–15.5, P < 0.001). In conclusion, oxidative stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some antioxidant markers could be a protective response of the eye against oxidative stress.

BackgroundDifferences in the expression of oxidative stress (OS) markers between female patients with temporomandibular disorders (TMD) and healthy individuals indicate that OS plays a role in the pathogenesis of TMD. Because chronic exposure to stress generates oxidative damage during continuous stimulation of the hypothalamic-pituitary-adrenal axis, we expected that higher levels of cortisol might be associated with higher oxidative damage. Our aim was to test the association between OS markers, stress perception, and salivary cortisol (SC) in chronic, female TMD patients. We tracked changes in OS markers and SC during occlusal splint therapy in order to evaluate the influence of treatment on oxidative status. We hypothesized that the effects of TMD therapy would differ among individuals depending on the source and intensity of pain.MethodsSixteen female patients were recruited, and 12 finished the study. Clinical assessment and saliva sampling were performed at the baseline and follow-up appointments. Repeated measures analysis of variance and Pearson’s correlation were used for analyzing the data.ResultsAfter 3 months, a significant reduction in afternoon total antioxidant capacity (TAC) was observed (p < 0.05). A significant reduction in afternoon malondialdehyde (MDA) (p = 0.021) and a decrease in afternoon MDA to superoxide dismutase ratios (p = 0.017) were present in high-intensity pain patients. At baseline, higher levels of perceived stress were significantly associated with higher morning cortisol (ρ = 0.67). At the end of the therapy, reduced perceived stress was positively correlated with morning SC changes when considering all TMD patients, but the association between perceived stress with OS markers was present only in myofascial pain (MP) group. The effect of treatment on the self-perceived quality of life was more pronounced in female MP patients while the reduction of spontaneous pain was significantly greater in high-intensity pain patients.ConclusionOur data indicate that occlusal splint therapy in female TMD patients contributes to increasing their capacity to remove free radicals. The question remains whether or not TAC decreases in this process as a result of avoiding unnecessary processes, once the increase in antioxidants effectively compensates for OS. The intensity and the source of pain should be considered important factors in future investigations evaluating salivary OS markers and their association with perceived stress and SC in TMD patients.Trial registrationClinicalTrials.gov NCT03029494. Registered on 2017-01-19.

Aim: Endoparasitic infections have long posed a significant threat to the sheep industry, leading to substantial economic losses. Among these parasites, Dicrocoelium dendriticum and, particularly, Echinococcus granulosus are globally important zoonotic parasites. This study aimed to investigate the levels of oxidative stress markers, antioxidant parameters, interleukins, and biochemical indicators, as well as their correlations, in sheep affected by cystic echinococcosis and dicrocoeliosis. Methods: In this study, various biochemical and immune-related parameters were assessed. Serum samples collected from infected sheep were analyzed using ELISA to measure interleukin-18 (IL-18), interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), NGAL, neopterin, myeloperoxidase, SOD, GPX, catalase, GSH, and MDA. Additionally, spectrometric analysis was performed to determine the levels of AST, ALT, GGT, albumin, globulin, total protein, ALP, and iron. Results: Serum MDA levels were found to be significantly elevated in infected sheep compared to the healthy group. In contrast, serum SOD and GSH levels in infected sheep were significantly lower than those in healthy sheep. Additionally, serum AST and ALT activities were markedly higher in the infected group. Interleukin levels showed no significant differences between the two groups. Overall, markers of liver function and oxidative stress were notably increased in infected sheep. Conclusion: It was concluded that oxidative stress and liver damage occurred in the infected group, and their immune system was actively involved in the response. This study not only adds to academic knowledge, but should also help veterinarians and breeders working in the field to make more accurate decisions. Thus it is expected to contribute directly to herd health, animal welfare, economic efficiency, and public health. Correlation data may also be useful in guiding the treatment process.

Clinical symptoms of syphilis are the consequence of the spirochete propensity to induce persistent chronic inflammation, which could participate to oxidative stress increase. The present study was designed to evaluate the level of oxidative stress biomarkers and antioxidant defences in a cohort of syphilitic patients. Serum oxidative status was explored in 63 patients diagnosed with early syphilis, 34 consulting patients negative for syphilis and 19 healthy controls. Total plasma thioredoxin (Trx) and thiols were determined as antioxidant capacity markers, °NO, advanced oxidation protein products (AOPP) and protein carbonyl levels as oxidative stress status biomarkers, and CRP as marker of inflammation. Mean serum levels of Trx, AOPP, carbonyls, and nitrates/nitrites were significantly higher, whereas thiols level was lower in syphilitic patients compared to non-syphilitic patients and healthy controls (respectively, p<0.05/p<0.01 for Trx, p<0.005/p<0.0001 for AOPP, p<0.05/p<0.005 for carbonyls, p<0.005/p<0.05 for nitrates/nitrites and p<0.01/p<0.0001 for thiols). According to the stage of the disease, results highlighted a marked and sustained oxidative stress imbalance from the first stage to the latent period of the disease. Moreover, syphilitic patients presented a low inflammation status reflected by median of CRP level (1.7mg/L, range 5th-95th percentile from <0.1 to 33.7mg/L), correlated with antioxidant capacity decrease (thiols) at stage 1 (r=-0.725; p<0.0001) and nitrosative stress increase (nitrates/nitrites) at stage 2 and latent (respectively, r=0.285, p<0.05 and r=0.650, p<0.05). These findings indicate that at all stages of the disease, despite a low-grade inflammatory state, syphilis infection generates a major oxidative and nitrosative stress which may be involved in the pathophysiology of the disease.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

Persons with Down syndrome have increased vulnerability to oxidative stress caused by overexpression of superoxide dismutase, an antioxidant enzyme coded on chromosome 21. Increased oxidative stress may lead to oxidative damage of important macromolecules. We monitored this damage by measuring levels of different biomarkers of oxidative stress (protein carbonyls and 4-hydroxy-2-nonenal), as well as plasma antioxidant capacity, in children with Down syndrome. A total of 20 children with Down syndrome and 18 healthy individuals were recruited for this purpose. Plasma protein carbonyls were measured using an ELISA technique, 4-hydroxy-2-nonenal was monitored by HPLC and the antioxidant capacity was evaluated using a ferric reducing ability of plasma (FRAP) assay. We found that children with Down syndrome had significantly elevated levels of protein carbonyls compared to healthy controls (p < 0.01). Levels of 4-hydroxy-2-nonenal and antioxidant capacity were similar in both groups. Our results on oxidative damage to proteins confirm the assumption of increased oxidative stress in individuals with Down syndrome.

Purpose: Aging is related to multiple and systemic dysfunctions in the body, accompanied by metabolic disorders and oxidative stress. Although studies are revealing the role of endoplasmic reticulum (ER) stress in aging-related pathologies, this relationship has not been fully elucidated. In this study, it was aimed to reveal changes in liver function, plasma lipids, and oxidative stress markers due to aging and gender, and to investigate how these parameters change with ER stress inhibitor tauro-ursodeoxycholic acid (TUDCA) treatment. Materials and Methods: Young (4 months old) and old (24 months old) Wistar albino male and female rats were used in the experiments. The administration of ER stress inhibitor TUDCA was performed for 4 weeks (150 mg/kg/day, ip). Liver function markers (AST and ALT), plasma lipids (LDL, HDL, TG and total cholesterol), and oxidative stress biomarkers (malondialdehyde, (MDA) and myeloperoxidase (MPO)) levels were measured in plasma samples. Results: ER stress inhibition with TUDCA decreased AST levels, increased HDL value, decreased TG value, and decreased MDA and MPO levels in the elderly. The effects on some parameters varied depending on gender. Conclusion: Considering the role of oxidative stress and metabolic disorders in the pathogenesis of many age-related diseases, it is thought that these results will contribute to the development of treatment approaches targeting ER stress inhibition in aging.

Objective: The objective of the study is to investigate the association between oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of the resistance in body to oxidative damage) in the cord blood of preterm low birth weight (LBW) neonates. Methods: Malondialdehyde (MDA), carbonyl proteins, total antioxidant capacity and Vitamin A, E and C levels in the cord blood were determined by spectrophotometry. Results: Increased lipid peroxidation, protein oxidation with decreased values of vitamin A, E, C and total antioxidant capacity were observed in the preterm LBW newborns. Observations of negative correlation between MDA and protein carbonyl with antioxidants vitamin A, E and C and total antioxidant status points towards the existence of oxidative stress in the preterm LBW newborns. Conclusions: Poor fetal growth affects the development of antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative stress, which in turn may partly account for increased morbidity and mortality in these infants. The presence of an association between oxidative stress biomarkers and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW neonates suggest that increased oxidative stress may be the result of changes in the levels of certain enzymatic and non-enzymatic antioxidants due to the cause or the effect of oxidative damage occurring at the molecular level.

PQQ has anti-inflammatory and anti-oxidant effects. PQQ can relieve high glucose-induced renal cell damage by suppressing Keap1 expression. Keap1 can interact with CUL3. Upregulation of CUL3 facilitates the apoptosis of LPS-induced podocytes. Based on knowledge above, this current work was designed to explore the role of PQQ in sepsis and determine the molecular function of CUL3 in the pathogenesis of sepsis. Rats received CLP surgery to establish sepsis models in vivo. Kupffer cells were pretreated with PQQ (10, 50 and 100 nmol/L) for 2 h and then treated with 100 ng/mL LPS for 24 h, simulating sepsis-induced acute liver injury in vitro. H&E staining was performed to evaluate liver injury of SD rats. Levels of inflammatory factors and oxidative stress markers were detected to assess inflammatory response and oxidative stress. Moreover, TUNEL staining, flow cytometric analysis and western blot were applied to determine cell apoptosis. It was confirmed that PQQ treatment relieved acute liver injury, inflammatory and oxidative stress damage and apoptosis of liver tissue cells in sepsis rats. In addition, PQQ therapy could alleviate inflammation, oxidative stress and apoptosis in LPS-induced Kupffer cells. Notably, LPS stimulation enhanced CUL3 expression and PQQ repressed CUL3 expression in Kupffer cells suffered from LPS. Overall, CUL3 overexpression weakened the remission effects of PQQ on LPS-induced inflammatory and oxidative damage and apoptosis of Kupffer cells. Mechanistically, PQQ treatment may mitigate sepsis-induced acute liver injury through downregulating CUL3 expression.