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• L-FABP is a novel biomarker for the early detection of abdominal injury and of hemorrhagic shock. • L-FABP is specific in the detection of an injury of the kidney and liver. • NGAL is a novel biomarker for the detection of abdominal injury and hemorrhagic shock. • NGAL failed to be specific in the detection of an injury of the liver and/or the kidney. Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l -FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l -FABP and NGAL are specific markers for detection of liver and/or kidney injuries. Traumatized patients with an age ≥18 years and an abdominal injury (AIS abd ≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l -FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. All patient groups had a median ISS≥25. In ER, median l -FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8–88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0–235.5]), p <0.001. In matched-pair-analysis l -FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l -FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l -FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l -FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6–163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0–89.6], p <0.001) and "Abd" group (70.5 ng/ml [IQR=53.3–115.5], p <0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. : L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l -FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same. [ABSTRACT FROM AUTHOR]

• CKD is now recognized as a distinct risk factor for CVD. • This risk rises in tandem with the decline in kidney function and peaks at the end stage. • This review presents an update on markers, which facilitate the prediction of CKD progression. Chronic kidney disease (CKD) is defined by gradual deterioration of the renal parenchyma and decline of functioning nephrons. CKD is now recognized as a distinct risk factor for cardiovascular disease (CVD). This risk rises in tandem with the decline in kidney function and peaks at the end-stage. It is important to identify individuals with CKD who are at a higher risk of advancing to end-stage renal disease (ESRD) and the beginning of CVD. This will enhance the clinical benefits and so that evidence-based therapy may be started at the initial stages for those individuals. A promising biomarker must represent tissue damage, and be easy to detect using non-invasive methods. Current CKD progression indicators have difficulties in reaching this aim. Hence this review presents an update on markers studied in the last decade, which help in the prediction of CKD progression such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid-binding protein, cystatin-C, asymmetric dimethylarginine, symmetric dimethylarginine, endotrophin, methylglyoxal, sclerostin, uric acid, and miRNA-196a. Additional research is needed to determine the predictive usefulness of these indicators in clinical samples for disease development. Their utility as surrogate markers need to be explored further for the early identification of CKD progression. [ABSTRACT FROM AUTHOR]

Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis. [Display omitted] • L-FABP is a mediator of lipid metabolism and has been associated with liver injury. • Urinary L-FABP and MELD-Na were associated with 90-day mortality in patients with decompensated cirrhosis. • Urinary L-FABP correlates with ACLF grade and liver, coagulation and circulatory failures. • Moreover, urinary L-FABP was related to the development of ACLF. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with adverse short- and long-term outcomes. AKI is diagnosed by serum creatinine (SCr)-based consensus definitions that capture an abrupt decrease in glomerular filtration rate associated with AKI. However, SCr-based AKI definitions lack sensitivity and specificity for diagnosing structural kidney injury. Moreover, AKI is a heterogeneous condition consisting of distinct phenotypes based on its etiology, prognosis, and molecular pathways, and that may potentially require different therapies. SCr-based AKI definitions provide no information on these AKI phenotypes. This review highlights traditional and novel tools that overcome the limitations of SCr-based AKI definitions to improve AKI phenotyping. [ABSTRACT FROM AUTHOR]

The aim of this study was to confirm the renoprotective effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1 a (AT1 a ) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1 a expression, we used AT1 a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1 a +/- L-FABP +/- ). Male AT1 a +/- L-FABP +/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3 mg/kg) or low-dose (1 mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments. In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1 a expression in the adenine-induced renal injury model. [ABSTRACT FROM AUTHOR]

[Display omitted] • Surface-enhanced Raman spectroscopy (SERS) is employed to characterize two important acute kidney injury (AKI) biomarkers, chitinase 3-like 1 (CH3L1) and liver fatty acid binding protein (L-FABP). • GO/Au@Ag nanoparticles are used as SERS substrates. • Trace amount of CH3L1 and L-FABP were detected at levels as low as 1.21 × 10-8 mg/mL and 0.62 × 10-8 mg/mL, respectively. • The proposed method on multiple biomarker detection will greatly improve the early diagnosis and intervention of AKI. Chitinase 3-like 1 (CH3L1) and liver fatty acid binding protein (L-FABP) are promising biomarkers for the early diagnosis of acute kidney injury (AKI). Here, a highly sensitive method for the quantitative detection of CH3L1 and L-FABP by surface-enhanced Raman spectroscopy (SERS) based on graphene oxide/gold and silver core–shell nanoparticles (GO/Au@Ag NPs) was proposed. The results showed that such GO/Au@Ag substrate can achieve rapid sensing of CH3L1 and L-FABP with a wide response range (2 × 10-1 to 2 × 10-8 mg/mL and 1.2 × 10-1 to 1.2 × 10-8 mg/mL, respectively) and high sensitivity. The detection limits of CH3L1 and L-FABP were 1.21 × 10-8 mg/mL and 0.62 × 10-8 mg/mL, respectively. In addition, the simultaneous detection of the two biomarkers in serum was demonstrated, showing the feasibility of this method in the complex biological environment. The detection of CH3L1 and L-FABP will greatly improve the early diagnosis and intervention of AKI. [ABSTRACT FROM AUTHOR]

Aim of the work To assess urinary liver fatty acid binding protein (uL-FABP) levels and tissue expression (tL-FABP) in renal biopsies of active and inactive lupus nephritis (LN) patients and examine their relationship with disease characteristics. Patients and methods uL-FABP levels and tL-FABP expression were assessed in 75 systemic lupus erythematosus (SLE) patients; 25 active LN, 25 inactive LN and 25 SLE without LN as well as 10 matched healthy control. Results Mean age was 33.9 ± 6.7 years, disease duration 4.6 ± 2.4 years and were 66 females and 9 males. Patients with active LN had higher uL-FABP higher than patients with inactive LN and without LN. uL-FABP in patients with active and inactive LN significantly correlated with renal SLEDAI (r = 0.96, r = 0.92 respectively and p < 0.0001) and 24-h urinary protein (r = 0.97, r = 0.68 respectively and p < 0.0001) but negatively correlated with the estimated Glomerular Filtration Rate (r = −0.97, r = −0.84 respectively and p < 0.0001). uL-FABP significantly correlated with grade of renal biopsy in active and inactive LN (F = 155.6 and 40.7 respectively, p < 0.0001). L-FABP was highly expressed in renal tissue of LN patients; the tubules seemed to be the main location for tL-FABP staining. The uL-FABP levels significantly correlated with the chronicity index score of renal pathology (F = 17.6, p < 0.0001) and the expression of tL-FABP in active and inactive LN (F = 21.4 and 42.2 respectively, p < 0.0001). Conclusion Urinary and tissue L-FABP levels were associated with active renal disease. Urinary levels of L-FABP might be a potential non invasive marker for the presence of renal involvement in patients with SLE alternative to renal biopsy. [ABSTRACT FROM AUTHOR]

Study Objective: To examine the change in liver-type fatty acid-binding protein (L-FABP) levels in patients undergoing aortic arch surgery and the correlation between L-FABP and postoperative acute kidney injury. Design: Prospective observational study. Setting: Operating room of a general hospital. Patients: 36 adult patients. Interventions and Measurements: Urine samples were obtained to measure urinary L-FABP at initiation of cardiopulmonary bypass (CPB) and 5 minutes after termination of hypothermic circulatory arrest. Main Results: 22 (61.1%) patients developed acute kidney injury within a 48-hour period. L-FABP increases more than a thousand-fold were found. In patients who subsequently developed acute kidney injury, significant increases in L-FABP were noted from 2.9 (3.6) ng/mg of creatinine before CPB to 62.1 (995.6) ng/mg of creatinine 5 minutes after termination of circulatory arrest. Values in patients who did not develop acute kidney injury increased from 1.1 (5.7) ng/mg before CPB to 1133.0 (6358.8) ng/mg of creatinine showing a significant mean difference (P = 0.011). The area under the L-FABP receiver operating characteristic curve at 5 minutes after termination of circulatory arrest was 0.758. A cutoff value of 75.13 ng/mg of creatinine yielded both good sensitivity (1.000) and specificity (0.546) for detecting non-acute kidney injury. Patients who developed acute kidney injury after aortic arch surgery demonstrated lower levels of urinary L-FABP. Conclusions: Low levels of urinary L-FABP may indicate kidney injury and lack of renal protection. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Acute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB. Design and methods: We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery. Results: Of the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2–48h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively). Conclusions: sCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome. [Copyright &y& Elsevier]

Abstract: Although liver fatty acid binding protein (L-FABP) binds fibrates and PPARα in vitro and enhances fibrate induction of PPARα in transformed cells, the functional significance of these findings is unclear, especially in normal hepatocytes. Studies with cultured primary mouse hepatocytes show that: 1) At physiological (6mM) glucose, fibrates (bezafibrate, fenofibrate) only weakly activated PPARα transcription of genes in LCFA β-oxidation; 2) High (11–20mM) glucose, but not maltose (osmotic control), significantly potentiated fibrate-induction of mRNA of these and other PPARα target genes to increase LCFA β-oxidation. These effects were associated with fibrate-mediated redistribution of L-FABP into nuclei—an effect prolonged by high glucose—but not with increased de novo fatty acid synthesis from glucose; 3) Potentiation of bezafibrate action by high glucose required an intact L-FABP/PPARα signaling pathway as shown with L-FABP null, PPARα null, PPARα inhibitor-treated WT, or PPARα-specific fenofibrate-treated WT hepatocytes. High glucose alone in the absence of fibrate was ineffective. Thus, high glucose potentiation of PPARα occurred through FABP/PPARα rather than indirectly through other PPARs or glucose induced signaling pathways. These data indicated L-FABP's importance in fibrate-induction of hepatic PPARα LCFA β-oxidative genes, especially in the context of high glucose levels. [Copyright &y& Elsevier]

Abstract: Background: To evaluate the value of basal urinary L-FABP (uL-FABP) excretion as a prognostic indicator of the progression of kidney function impairment in patients with chronic glomerulonephritis (CGN). Methods: One hundred twenty-three patients with newly diagnosed, biopsy-proven primary CGN were included. In all patients, and in 28 healthy subjects, uL-FABP was measured using an ELISA. Risk factors of the progression of kidney function were evaluated. The patients were in follow-up for at least 5years. Results: uL-FABP in the patients with CGN (76.58±17.3μg/g.cr) was greater than in the healthy subjects. A significant positive correlation between uL-FABP and proteinuria (R=0.501, P<0.01), serum creatinine (R=0.601, P<0.01) were found. Kaplan–Meier analysis revealed that uL-FABP >76.58μg/g.cr predicts progression of renal function. The cut off values for L-FABP at 119.8μg/g.cr was found to be more sensitive, area under the curve (AUC) was 0.95. Conclusion: Urinary L-FABP may be a useful clinical biomarker for monitoring chronic glomerular disease. Urinary L-FABP can help predict the progression of chronic glomerular disease. [Copyright &y& Elsevier]

Abstract: In fatalities with multiple traumatic injuries, it is important to determine the severity of trauma, the main damaged organ, and the antemortem pathophysiological condition. We examined 63 cases within 48h of the postmortem interval, which included assaults, slips and falls and falls from heights, traffic accidents, and sharp instrumental injuries. Immunohistochemically, each kidney was stained against hemoglobin (Hb), myoglobin (Mb), superoxide dismutase (SOD), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 150kDa oxygen regulated protein (ORP150), pulmonary surfactant A (SP-A), and liver-type fatty acid binding protein (L-FABP). Bleeding or circulatory failure induced ORP150, 8-OHdG, and L-FABP in the kidney. Statistical analysis of the immunoreactivity revealed that in battered and/or abused cases, Hb could be considered a specific marker. Hb and Mb were observed in the cases with general severe trauma, such as slips and falls and falls from heights. In traffic accidents, ORP150 could reflect general circulatory failure with bleeding. SP-A was observed in the cases with severe thoracic injuries, such as lung injuries and multiple thoracic fractures. L-FABP appeared in cases with renal circulatory failure as well as renal injury. These findings suggest that immunohistochemical observation of the kidneys could be a useful tool in determining several key factors, such as the severity of injury, the specific damaged organ, and the pathological condition after injury. [Copyright &y& Elsevier]

Abstract: TroponinC2 (TNNC2), a constituent of the troponin complex located on the thin filament, plays a critical role in skeletal muscle contraction and improving meat quality traits of livestock and poultry. The TNNC2 gene has been identified in many mammals, but very little known about goat. In the study, we cloned TNNC2 gene in goat for the first time and analyzed its tissue expression. Results indicated that TNNC2 contains 483bp CDS and encodes 160 amino acids, and it was selectively expressed in the muscular tissues of goat. Its nucleotide sequence was high similar with sheep (93.38%) and alpaca (90.48%), and the identity of encoded amino acids which was varied from 100% (sheep) to 70.81% (Atlantic salmon) in animal. We found that the Ala113 and leu132 was distributed very law in mammals. The amino acid residue of Ca2+ binding sitesNSimSun.1.10was identical in mammalsSimSun.2.200Aves and amphibian. This study may provide more insight into the molecular structure and expression patterns of the vertebrate TNNC2 gene. [Copyright &y& Elsevier]

Abstract: In order to understand the structure and function of L-FABP gene, reveal the effect on the fatty acid binding in goat, and find the molecule marker correlated with meat traits, the cDNA of L-FABP gene was cloned and sequenced from liver of goat by T-A clone techniques. The structure and function of L-FABP were analyzed by bioinformatics, and the gene expression profile in different tissues was examined by real-time PCR. The results showed that the full sequence of L-FABP cDNA is 405bp, containing 384bp coding region (CDS) encoding 127 amino acids. The secondary structure of the protein was mainly α-helixes, extended strands and β-turns structure. The deduced amino acid sequence of L-FABP shared significant identity with the L-FABP from other mammals. The phylogenic tree based on L-FABP protein sequence was detected the closest relationship between cattle and pig. A predicted 3D model was constructed by homology modeling. An L-FABP specific product was generated by RT-PCR in various tissues, the amount of L-FABP mRNA in liver and kidney was higher than in heart and skeletal muscle, and it was faintly detected in lung. [Copyright &y& Elsevier]

Background/Aims: Bacterial infection combined with hypotension results in exacerbation of the inflammatory response with release of interferon (IFN) gamma. This excessive inflammation may lead to development of hepatic damage and liver failure. This study investigates the effect of dietary lipids on release of IFN-γ and development of hepatic damage following exposure to synthetic bacterial DNA (CpG-ODN) and hemorrhagic shock. Methods: Rats were exposed to CpG-ODN 18h before hemorrhagic shock. Samples were taken 4h following shock. High-fat nutrition was administered at 18h, 2h and 45min before induction of shock. Results: Enteral high-fat strongly reduced circulating IFN-γ (0.2ng/ml, P <0.01) following exposure to CpG-ODN and hemorrhagic shock compared with fasted rats (2.7ng/ml). Concomitantly, plasma L-FABP was reduced (437±22ng/ml, P <0.01), and F-actin distribution was preserved. Furthermore, high-fat nutrition reduced apoptosis in the liver and preserved expression of the hepatoprotective protein ABIN-1. Interestingly, administration of anti-IFN-γ antibodies was associated with reduced expression of ABIN-1. Conclusions: This study shows that enteral high-fat reduces IFN-γ and decreases CpG-enhanced liver injury following hemorrhagic shock. Administration of high-fat nutrition may be an important new therapeutic strategy to reduce liver damage in a clinical setting of bacterial infection combined with hypotension. [Copyright &y& Elsevier]

: ObjectivesIntestinal-type fatty acid-binding protein (I-FABP) has been proposed as plasma marker for the detection of acute intestinal injury. However, intestinal mucosa also expresses liver-type FABP (L-FABP). We have investigated the tissue distribution of I-FABP and L-FABP in segments of the human intestine along the duodenal to colonal axis and the potential of both proteins to serve as plasma marker for the diagnosis of intestinal injury.: Design and methodsI-FABP and L-FABP were measured with specific immunoassays in autopsy samples of the intestine (duodenum, jejunum, ileum and colon) of 23 subjects and in plasma samples from patients (n = 51) with intestinal and/or hepatic disease. Plasma reference values were established in normal healthy individuals (n = 92).: ResultsThe I-FABP tissue contents in duodenum, jejunum, ileum, proximal colon and distal colon amounted to 2.22, 4.79, 1.04, 0.27 and 0.25 μg/g ww, respectively. L-FABP tissue contents were markedly higher, amounting to 124 and 198 μg/g ww in duodenum and jejunum, and to 58, 26 and 44 μg/g ww in ileum, proximal colon and distal colon, respectively. Elevated plasma levels of both I-FABP and L-FABP were found in patients suffering from intestinal diseases, while only L-FABP was increased in cases of purely hepatocellular injury.: ConclusionsI-FABP and L-FABP show a similar pattern of tissue distribution along the duodenal to colonal axis with highest tissue contents found in the jejunum but in each intestinal segment a >40-fold higher content of L-FABP than of I-FABP. Accordingly, besides I-FABP, also L-FABP is a useful plasma marker for the detection of intestinal injury, especially in patients undergoing intestinal surgery. [Copyright &y& Elsevier]

• Liver ischemia reperfusion injury is an unavoidable problem, still a challenge. • Diacerein exhibits anti-inflammatory, anti-apoptotic and antioxidant properties. • Liver fatty acid binding protein, an effective marker to detect early liver damage. • Adhesion molecule accepted to be a cornerstone in ischemia reperfusion injury. • Diacerein could ameliorate the signaling mechanisms underlying this pathophysiology. Liver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. Adult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. Diacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. These results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway. [ABSTRACT FROM AUTHOR]