Serum ALP Research Articles

Prognostic significance of the urokinase plasminogen activator system in tissue and serum of dogs with appendicular osteosarcoma.

Urokinase plasminogen activator (uPA) and its receptor uPAR promote cancer invasion and metastasis and are emerging therapeutic targets in both human and canine malignancies. While their clinical significance is well-characterized in multiple human tumor types, studies investigating their roles in osteosarcoma are lacking. The objectives of this study were to characterize serum and tissue uPA/uPAR expression in dogs with osteosarcoma and assess the prognostic significance. Serum samples and a tissue microarray of canine appendicular osteosarcoma were analyzed for uPA and uPAR expression by ELISA (n = 49) and immunohistochemistry (n = 38), respectively. Serum uPA activity was also measured by a chromogenic assay (n = 25). Survival analysis was performed by Kaplan-Meier survival analysis, log rank test, and Cox regression analysis. Serum uPA level was significantly higher in dogs with osteosarcoma than clinically healthy control dogs (median 1905 vs 1440 pg/ml, p = 0.008). The majority of canine osteosarcoma tissues expressed uPA (75.9%) or uPAR (77.6%), with 70.7% dual-positivity, indicating autocrine/paracrine activation of the pathway. Survival analysis revealed shorter progression free survival (PFS) in dogs with high serum uPA level in a discovery cohort (n = 29; median PFS 94 vs 266 days, p = 0.003) but not in a validation cohort (n = 23; median PFS 167 vs 490 days, p = 0.16). The difference was significant when both cohorts were combined (n = 49; median PFS 128 vs 266 days, p = 0.003). Serum uPAR and tissue uPA/uPAR levels were not prognostic. In Cox multivariate analysis, high serum uPA level and activity were both associated with poor prognosis, independent of serum ALP, tumor location, and peripheral lymphocyte/monocyte counts. These results indicate high utilization of the uPA pathway and association with disease progression in canine osteosarcoma. Further study involving prospective evaluation to confirm the prognostic significance is warranted. The high prevalence of tissue uPA and uPAR expression suggests the uPA system as a potential therapeutic target in canine osteosarcoma.

Low gamma-glutamyl transpeptidase levels at presentation are associated with severity of liver illness and poor outcome in biliary atresia.

ObjectiveTo investigate the clinical features and prognosis of biliary atresia (BA) with normal or minimally elevated gamma-glutamyl transpeptidase (GGT).MethodsThe clinical data of patients with BA in our hospital between 2012 and 2017 were retrospectively studied. The patients were divided into a low-GGT group (GGT ≤ 300 IU/L) and a high-GGT group (GGT > 300 IU/L) according to the preoperative GGT level. The perioperative clinical parameters, the postoperative jaundice clearance within 6 months, and the 2-year native liver survival were compared among the groups.ResultsA total of 1,998 children were included in this study, namely, 496 in the low-GGT group and 1,502 in the high-GGT group. The ages and weights at the surgery in the low-GGT group were significantly lower than those in the high-GGT group (64.71 ± 21.35 vs. 68.64 ± 22.42 days, P = 0.001; 4.67 ± 1.03 vs. 4.89 ± 0.98 kg, P < 0.001). The levels of serum ALP, ALT, and AST in the low-GGT group were significantly higher than those in the high-GGT group before and 2 weeks after the surgery (ALP: 647.52 ± 244.10 vs. 594.14 ± 228.33 U/L, P < 0.001; ALT: 119.62 ± 97.14 vs. 96.01 ± 66.28 U/L, P < 0.001; AST: 218.00 ± 173.82 vs. 160.71 ± 96.32 U/L; P < 0.001). The INR of the low-GGT group was higher than that of the high-GGT group (1.05 ± 0.34 vs. 0.98 ± 0.20, P < 0.001), while FIB was lower than the high-GGT group (2.54 ± 0.67 vs. 2.73 ± 1.44 g/L; P = 0.006). The decreasing amplitude of TB and DB within 2 weeks after surgery in the low-GGT group was smaller than those in the high-GGT group (TB: 51.62 ± 71.22 vs. 61.67 ± 53.99 μmol/L, P = 0.003; DB: 33.22 ± 35.57 vs. 40.20 ± 35.93 μmol/L, P < 0.001). The jaundice clearance rate in the low-GGT group was significantly lower than that in the high-GGT group at 1, 3, and 6 months after surgery (17.70 vs. 26.05%; 35.17 vs. 48.58%; 38.62 vs. 54.64%, P < 0.001). In addition, the 2-year native liver survival rate in the low-GGT group was significantly lower than that of the high-GGT group (52.5 vs. 66.3%, P < 0.001 HR 1.80, 95% CI 1.38–2.33).ConclusionCompared to patients with high GGT, patients with normal or minimally elevated pre-operative GGT in BA were found to have poorer pre-operative liver function parameters, and post-operatively had lower jaundice clearance rates and worse 2-year native liver survival. This suggests a lower GGT at presentation in biliary atresia could be a sign of more severe liver injury.

Assessment of copper and zinc in liver diseases

The liver is a primary storage site for a variety of metabolites. It plays a role in wide variety of metabolic, toxic, excretory, circulatory and defence functions inside the body. Damage to the organ may not evidently affect its activity since the liver has considerable functional reserve. Liver disease is a common term for any damage that reduces the functioning of the liver. Chronic liver disease is identified by gradual destruction of liver cells resulting in fibrosis. It is affected by different conditions including viral hepatitis, excessive alcoholism, genetic, autoimmune and NAFLD. The present study was carried out in Govt. Medical College, Jalaun at Department of Biochemistry. The diagnosis of Liver disease was done by ultrasonographic examination of liver. This study comprised a total of 50 patients, 25 of whom were healthy controls and 25 of whom were Liver Disease patients. After overnight fasting 8-12 hours (under aseptic condition) blood sample (8ml) was drawn from antecubital vein of each subject using a plain vial and was analyzed for serum Cu, Zn &amp; liver profile parameters (serum bilirubin, serum SGOT, serum SGPT and serum ALP done by colorimetric method and calmagnite method, diazo method, IFCC method and assessed by kinetic method respectively. The present study’s findings, indicates that the level of serum copper in liver disease patient was 127.38±28.81µg/dl, which is significantly higher than that of 86.54 ± 15.88µg/dl found is healthy controls (p&amp;#60;0.001). Also, serum copper is strongly linked with biochemical parameters of liver enzyme (SGOT &amp; SGPT). Likewise, the mean value of serum zinc in liver disease were 58.08 ± 13.11µg/dl, which is significantly lower than that of69.88± 6.67µg/dl found in healthy subjects. Further, serum zinc has shown a significant weakly linked with serum SGPT.Therefore, during routine assessments of individuals with liver disease, serum trace elements (Cu and Zn) can be highly effective indicators for detecting the severity of liver damage. Thus, based on the findings of our current investigation, zinc and copper supplementation, as well as a reduction in copper intake, may help to enhance patient survival and preventing the development of hepatitis B to liver cirrhosis.Considering findings of the study, it is recommended that serum trace element concentrations be corrected on a regular basis to help with various problems of liver cirrhosis and maybe to slow the progression of liver disease.

Anti-apoptotic properties of N-Acetyl cysteine and its effects on of Liver X receptor and Sirtuin 1 expression in the liver of rats exposed to Lead

BackgroundThis study aimed to evaluate the expression of Liver X receptor (Lxr), Sirtuin 1 (Sirt1), apoptotic-related genes, and the protective role of N-acetylcysteine (NAC) in the liver of rats treated with Lead (Pb). MethodsRats were randomly divided into 5 groups, including G1 (control), G2 (single dose of Pb), G3 (continuous dose of Pb), G4 (single dose of Pb + NAC), and G5 (continuous dose of Pb + NAC). Lipid profiles and liver specific enzymes were assessed. Expression of Lxr, Sirt1, Bax and Caspase-3 genes was considered using RT-PCR. ResultsExposure to Pb caused a significant accumulation of Pb in the blood and liver tissue, increase in serum AST, ALT and ALP enzymes, as well as lipid profiles. Chronic exposure to Pb caused a significant decrease in Lxr (3.15-fold; p < 0.001) and Sirt1 (2.78-fold; p = 0.009), but significant increase in expression of Bax (4.49-fold; p < 0.001) and Caspase-3 (4.10-fold; p < 0.001) genes when compared to the control. Combined therapy with Pb + NAC in rats caused a significant decrease in AST, ALT and ALP values (28.93%, 20.80% and 28.86%, respectively) in the blood as compared to rats treated with Pb alone. Co-treated with Pb + NAC significantly increased the expression of Lxr (1.72-fold; p = 0.043) and Sirt1 (2.45-fold; p = 0.008), but decreased the expression of Bax (1.96-fold; p = 0.03) and Caspase 3 (2.22-fold; p = 0.029) genes when compared to rats treated with Pb alone. ConclusionChronic exposure to Pb is strongly associated with accumulation of Pb in the blood and liver, hepatic cells apoptosis, down-expression of Lxr and Sirt1 genes and consequently liver injury and abnormal lipid profiles. NAC reversed the Pb-induced toxicity on the liver tissue.

Peptide-Calcium Chelate from Antler (Cervus elaphus) Bone Enhances Calcium Absorption in Intestinal Caco-2 Cells and D-gal-Induced Aging Mouse Model.

Antler bone calcium (AB−Ca) and bioactive peptides (ABPs) were extracted from antler bones (Cervus elaphus) to maximize their value. In this study, 0.14 g calcium was obtained from 1 g antler bone. The peptide−calcium chelate rate was 53.68 ± 1.80%, and the Gly, Pro, and Glu in ABPs were identified to donate most to the increased calcium affinity through the mass spectrometry. Fourier transform infrared spectroscopy showed that calcium predominantly interacted with amino nitrogen atoms and carboxyl oxygen atoms, thereby generating a peptide–calcium chelate. The peptide−calcium chelates were characterized using scanning electron microscopy. A Caco-2 cell monolayer model showed that ABPs significantly increased calcium transport. Furthermore, the D-gal-induced aging mouse model indicated that the ABPs + AB−Ca group showed higher Ca and PINP levels, lower P, ALP, and CTX-1content in serum, and considerably higher tibia index and tibia calcium content. Results showed that ABPs + AB-Ca increased bone formation and inhibited bone resorption, thereby providing calcium supplements for ameliorating senile osteoporosis (SOP).

Is Sevelamer Carbonate Better Than Calcium Acetate in ControllingChroni Kidney Disease-Mineral Bone Disease in Dialysis Patients

Objective: To ascertain the efficacy of Sevelamer Carbonate as a better phosphate binder for controlling mineral bone disease biochemical parameters in dialysis patients of a tertiary care centre compared to calcium acetate.&#x0D; Study Design: Prospective Quasi-experimental study.&#x0D; Place and duration of the study: Dialysis unit of Pakistan Emirates Military Hospital Rawalpindi Pakistan from Aug to Dec 2020.&#x0D; Methodology: The sample population comprised 91 patients undergoing maintenance thrice weekly haemodialysis patients treated with Sevelamer Carbonate or Calcium Acetate. CKD-MBD was assessed by serum calcium, phosphorus, ALP, albumin and PTH at the start of the study and then at the end of three months after being treated with phosphate binders.&#x0D; Results: Both Groups had reduced serum phosphorus significantly from baseline to 12 weeks but Sevelamer slightly more than calcium acetate. (Group-1 from 6.90±1.35 to 5.10±1.21, while Group-2 from 7.00±1.31 to 5.90±1.48). The mean Calcium × Phosphorus product was also significantly reduced (p&lt;0.005), decreases after 12 weeks, with 50.0 ± 16.0 in the Sevelamer Hydrochloride Group and insignificantly reduced (52.20±5.20mg2/dl) in the calcium acetate Group. The mean serum calcium increased significantly in the calcium acetate Group from 9.55±0.47 to 10.50±0.90) p=0.003 but was unchanged in the Sevelamerhydrochloride Group (9.56±0.60 to 9.57±0.67; p=0.94).&#x0D; Conclusions: CKD-MBD and its sequelae need special medication, and early detection of biochemical abnormalities and timely intervention with phosphate lowering therapy can abridge the disease burden, thus revamping the quality of life and ultimately abatement of cardiovascular morbidity and mortality.

Serum asprosin levels in patients with retinopathy of prematurity

Abstract Objectives This study was aimed to investigate the diagnostic values of serum levels of asprosin and neutrophil gelatinase-associated lipocalin (NGAL) in Retinopathy of prematurity (ROP) and to assess the role of these biomarkers on the development and progression of the condition. Methods This study was carried out from April 2020 to February 2021 in the department of ophthalmology of a tertiary hospital in Turkey. Thirty patients diagnosed with ROP and 30 healthy newborns were included the study. Serum NGAL and asprosin levels were determined via ELISA. Results The median serum NGAL levels were found to be similar between the ROP group and the control group (p=0.595). Median asprosin levels were significantly higher in patients diagnosed with ROP [46.58 (12.70–142.28) ng/mL] compared to healthy subjects [13.05 (10.92–17.73) ng/mL] (p=0.001). The optimal cut-off value of asprosin by ROC analysis was 30 ng/mL (AUC: 0.754, p=0.001) for diagnosing ROP. Serum asprosin levels were positively correlated with serum ALP levels and inversely correlated with gestational week, uric acid and AST values (all, p&lt;0.005). Conclusions Our results demonstrated that asprosin, but not NGAL, could be a biomarker for the diagnosis of ROP.

Mulberry leaves juice attenuates arsenic-induced neurobehavioral and hepatic disorders in mice.

Arsenic (As) poisoning has caused an environmental catastrophe in Bangladesh as millions of people are exposed to As-contaminated drinking water. Chronic As-exposure causes depression, memory impairment, and liver injury in experimental animals. This study was carried out to assess the protective effect of mulberry leaves juice (Mul) against As-induced neurobehavioral and hepatic dysfunctions in Swiss albino mice. As-exposed mice spent significantly reduced time in open arms and increased time spent in closed arms in the elevated plus maze (EPM) test, whereas they took significantly longer time to find the hidden platform in the Morris water maze (MWM) test and spent significantly less time in the desired quadrant when compared to the control mice. A significant reduction in serum BChE activity, an indicator of As-induced neurotoxicity-associated behavioral changes, was noted in As-exposed mice compared to control mice. Supplementation of Mul to As-exposed mice significantly increased serum BChE activity, increased the time spent in open arms and reduced time latency to find the hidden platform, and stayed more time in the target quadrant in EPM and MWM tests, respectively, compared to As-exposed-only mice. Also, a significantly reduced activity of BChE, AChE, SOD, and GSH in brain, and elevated ALP, AST, and ALT activities in serum were noted in As-exposed mice when compared to control mice. Mul supplementation significantly restored the activity of these enzymes and also recovered As-induced alterations in hepatic tissue in As-exposed mice. In conclusion, this study suggested that mulberry leaves juice attenuates As-induced neurobehavioral and hepatic dysfunction in mice.

The Relationship between the SUVmax Value Obtained in Ga-68 PSMA PET/CT and Lactate Dehydrogenase and Alkaline Phosphatase in Prostate Cancer.

ALP and LDH are serum markers of prognostic importance in prostate cancer patients. PET/CT imaging with Ga-68 PSMA has played an important role in prostate cancer imaging in recent years. Our aim in this study was to evaluate the relationship and prognostic significance between SUVmax values obtained with Ga-68 PSMA PET/CT and LDH and ALP levels in prostate cancer patients. We retrospectively evaluated 61 prostate cancer patients who had Ga-68 PSMA PET/CT imaging and who did not have a prostatectomy between 2019 and 2020. PSA, ALP and LDH levels were measured in all patients before or after imaging within a maximum of 28 days. The median age of the patients included in this study was 73 (range: 57-89) and all 61 patients were prostatic adenocarcinoma. 50 (82%) of the patients had distant metastasis in Ga-68 PSMA PET/CT. There was a significant positive correlation between serum LDH and PSA levels. There was a positive correlation between serum ALP and PSA levels. A negative correlation was found between ALP levels and prostate SUVmax. While negative correlation was found between SUVmax and ALP levels, no correlation was found between LDH levels and SUVmax. High ALP levels were found to be related to metastasis rates and severity and high serum PSA levels.

Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2.

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.

Ameliorative Effect of Tamarindus indica and Vitamin D Supplementation On Fluoride Induced Biochemical Parameters in Albino Rat

Fluoride water problem is very common in all areas of world including India. The deleterious effects of fluoride on bones causes fluorosis. This problem arises mainly due to gradual lowering of ground water level, which is merely responsible for degrading water quality. The hand pumps of many areas are restricted for use due to excess fluoride in their water. In a country like India, it is very tough to provide pure drinking water to all. Hence this study is designed to study the effect of fluoride on biochemical parameters in albino rats, the mammalian model. The aim and objective of this study is to evaluate combination of two antioxidants viz. Tamarindus indica (rich source of vitamin C) and vitamin D against fluoride toxicity in mammals for which albino rat is used as model. Tamarindus have significant amount of antioxidants and vitamin D also have immunity and healing properties, hence this can be a reason behind their cumulative ameliorative effect against sodium fluoride intoxication. Further, the effect of fluoride can be minimized or ameliorated using some antioxidants and vitamins. For this purpose, the fluoride intoxicated rats were observed for possible amelioration by Tamarindus indica and vitamin D supplementation. The fluoride intoxication showed altered biochemical parameters like serum protein, SGOT, SGPT, ACP, ALP and LDH

Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China.

BackgroundAlkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China.MethodsWe enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1–Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3–6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes.ResultsOverall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19–3.96; P = 0.011] and patients in Q3 (76.8–92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14–0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0–76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes.ConclusionNon-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 μg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 μg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels.

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE.Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Alleviation of cisplatin-induced hepatotoxicity and nephrotoxicity by L-carnitine.

Objective(s):To assess the protective effect of L-carnitine in reducing cisplatin toxicity via estimating biochemical tests, histomorphometric, and immunohistochemistry (IHC) of β-catenin and cyclin D.Materials and Methods: Fifteen adult male rabbits were used in this study and allocated into 3 groups; Group 1 (Control negative), rabbits of this group were not given any treatment. In group 2, the animals were injected with cisplatin single-dose/per week. Group 3 rabbits were treated with Cisplatin+L-carnitine orally by gavage tube for 29 days. At the end of the experiments, blood samples from all rabbits were taken from the earlobe, and then the biochemical test was done, the kidney and tissue sections were prepared for both H& E and IHC for both β-catenin and cyclin D genes.Results:Treatment with L-carnitine reduced the injury effect of cisplatin via a decline in serum creatinine, urea, bilirubin, GPT, GOP, and ALP significantly (P<0.05). Also, administration of LC attenuates the histopathologic abnormality in the kidney (15.71% vs 85.18%) and liver (score 3 vs 15 ) induced by cisplatin. L-carnitine elevates the expression of β-catenin and cyclin D in renal and hepatic parenchyma by diffuse, moderate-strong positivity vs cisplatin that showed local-weak staining.Conclusion:These findings imply that L-carnitine, by its pleiotropic actions in activating Wnt signaling, alleviates cisplatin-induced renal and hepatic destruction. It might be a method of preventing cisplatin-related nephrotoxicity and hepatotoxicity.

Antioxidant and hepatoprotective potentials of olive (Olea europaea L. var. Sigoise) leaves against carbon tetrachloride-induced hepatic damage in rats, and investigation of its constituents by high-performance liquid chromatography-mass spectrometry

The present work explored the preventive potential of ethanolic extract of Olea europaea L. (EEOE) leaves against CCl4-induced liver injury in rats. The fingerprint chromatogram of EEOE was determined by HPLC-MS analysis. The antioxidative potential of EEOE was determined by adopting three approved in vitro methods. The EEOE was orally given at a dose of 400 mg/kg, once a day, for 15 days continuously, succeeded by intraperitoneal (i.p.) injection of CCl4 (0.2%). The hepatoprotective potential was evaluated by estimating biochemical parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total cholesterol, and triglycerides in the bloodstream. In vivo, the antioxidant ability against CCl4-induced liver injury in rats was assessed by estimating the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total reduced glutathione, and lipid peroxidation in the liver tissues. Further, histological analyses were performed to evaluate the degree of hepatic damage. Nine compounds were identified in the EEOE, principally oleuropein, luteolin-7-O-glucoside, and apigenin. The EEOE exhibited strong radical scavenging activity in DPPH assay. The EEOE significantly decreased the augmentation of serum cholesterol, TG, ALT, AST, ALP, and total bilirubin contents. It also restored hepatic SOD, CAT, GSH-Px activities, and glutathione (GSH) amount, and lowered lipid peroxidation amount comparable to the standard silymarin. The biochemical data were complemented with histological conclusions. These findings are indicative of the protective potential of the EEOE against CCl4-induced hepatotoxicity, which is possibly related to the potent antioxidative capacity of its phenolic compounds.

Histopathological, immunohistochemical, and molecular investigation of atrazine toxic effect on some organs of adult male albino rats with a screening of Acacia nilotica as a protective trial.

Atrazine (ATZ) is a widely used herbicide; however, it has deleterious effects. The current study aimed to investigate the potential toxic effect of ATZ as a neuroendocrine disruptor on the cerebellum and thyroid gland and on the liver as a detoxifying organ. We examined the ability of ATZ to induce oxidative stress and subsequent apoptosis in these organs. Moreover, we investigated the potential protective effect of Acacia nilotica, because of its potent antioxidant activity. Thus, our study was carried out on 40 adult male albino rats that were divided equally into 4 groups (10 rats/each group). The first group received distilled water, while the second group received ATZ dissolved in corn oil at 200 mg/kg body weight/day by stomach gavage. The third group was treated orally by ATZ (200 mg/kg body weight/day) plus Acacia nilotica (400 mg/kg/day). Group IV received Acacia nilotica only at a dose (400 mg/kg/day). After successive 30 days of the experiment, blood and tissue samples were collected from all groups. Our findings revealed the ability of ATZ to induce toxic effects was observed microscopically in the form of degenerated neurons and vacuolated neuropil of the cerebellum, degenerated hepatocytes, and vacuolation of the follicular cells of the thyroid gland. Furthermore, ATZ significantly elevated AST, ALT, and ALP serum levels and TB concentration, while decreased GSH. DNA fragmentation% and activated caspase-3 expression significantly increased after ATZ exposure. Interestingly, Acacia nilotica administration was able to partially protect the examined organs against the toxic effect of ATZ exposure.

Abstract 3746: Influence of diethylnitrosamine on Mucin 13 expression in hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is regarded as environmental-related cancer due to involvement of chemical carcinogen and viral components in multistage process. Accumulating studies have shown that obesity and non-alcoholic fatty liver disease, which can lead to HCC, have been linked to modern diets that are high in fat and charcoal-grilled processed meat, however, the exact processes through which diet contributes to hepato-carcinogenesis remain unclear. In the present study, we demonstrated that diethylnitrosamine (DEN), a subgroup of the N-nitroso compounds presents in food additive/preservative, tobacco smoke, and pharmaceutical products, upregulates the Mucin 13, transmembrane mucin, via miR-145 suppression accompanied by hepatocarcinogenesis events. Methodology: Western blotting and qPCR were performed to examine the treatment effects of DEN on Mucin 13 and associated effector proteins in hepatocellular carcinoma cell (HepG2, Hep3B, C3A, and SK-HEP-1) lines. Chemically induced (DEN; 200 mg/kg bw; 2-AAF (150 mg/kg bw) animal model was used to further investigate the Mucin 13 expression. The serum AST, ALT and ALP activity were measured using kits provided by Span diagnostics. Immunohistochemistry was used to stain tumor tissue sections for Mucin 13 expression, and in situ hybridization was performed to detect miR-145 levels. Molecular docking studies were performed using Auto dock 4 package. Results: Our study demonstrated that DEN treatment facilitates the DNA adducts formation in liver cancer cell lines as compared to vehicle controls. Moreover, DEN treatment upregulates Mucin 13 and associated effector proteins as analyzed by qPCR and Western blotting. Liver section of DEN+2-AAF-administered group showed vacuolization of hepatocytes in the centrizonal area with variation of nuclear size. Clear nuclear atypia in the adenoma was seen. The serum activities of AST, ALP and ALT in diseased animals correlated with the liver cancer progression. Additionally, Mucin 13 was also upregulated by DEN treatment in liver tissues. Intriguingly, nuclear Mucin 13 staining was very less in normal liver tissues, whereas its levels were significantly increased DEN+2-AAF induced HCC. These observations indicate that nuclear localization of Mucin 13 may contribute to the malignant transformation of hepatocytes during carcinogenesis. This revealed significant downregulation of tumor suppressors miR-145 in tumor tissues as compared to normal control. Molecular modelling analysis revealed that DEN interacts with Mucin 13 and forms a stable complex by offering numerous interactions with the residues of Mucin 13. Conclusions: We propose that DEN modulates Mucin 13 and associated effector proteins in hepatocarcinogenesis. Citation Format: Shabnam Malik, Mohammed Sikander, Parvez Khan, Murali M. Yallapu, Swatantra Jain, Deepshikha P. Katare, Subhash C. Chauhan, Meena Jaggi. Influence of diethylnitrosamine on Mucin 13 expression in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3746.

Sodium benzoate in locally available soft drinks and its effect on DNA damage and liver function in rats

Sodium benzoate (E211) is used as a preservative in several kinds of food. One of the essential uses of E211 is to preserve non-alcoholic carbonated beverages. The amount of sodium benzoate in 17 local soft drink samples was estimated in the present study. The in vivo effects on biochemical aspects of the liver, kidney function, and DNA damage in lymphocytes were also investigated after oral administration of sodium benzoate in rats over 12 days. The control and experimental groups were fed standard pellet diet and distilled water ad libitum; and administered distilled water (control) and different concentrations (30, 60, and 120 mg/kg body weight) of sodium benzoate once daily through a stomach tube (0.5 ml), respectively. The alkaline comet assay was performed to investigate the possible DNA damage induced by E211 in lymphocytes. At the end of the experiment, after overnight fasting the rats were sacrificed and blood samples were collected. Animals showed no significant weight loss or gain. The investigation revealed that twelve samples contained a higher level, and the rest had trace or below the recommended maximum permitted concentration (150 mg/l) of E211 as a preservative in the soft drinks. The percentage of tail DNA (p &lt; 0.01) and olive tail movement (p &lt; 0.05) was significantly increased in lymphocytes that were treated with high concentration (120 mg/kg body weight) of sodium benzoate, indicated substantially higher DNA damage (3.5 times) in lymphocytes compared to control. Moreover, serum AST activity level was increased significantly (p&lt;0.05) in the group treated with a higher dose (120 mg/kg body weight) of E211, indicating malfunction of the liver. The preservative did not significantly affect serum ALT and ALP activity, total bilirubin, creatinine, and urea level. Nonetheless, our findings suggest that caution should be adopted for using sodium benzoate as a preservative in various food products. Dhaka Univ. J. Biol. Sci. 30(3 CSI): 371-383, 2022 (June)

Evaluation of Diagnostic Role of Alkaline Phosphatase in the Patients of Cerebral Stroke

Background: The cerebral stroke is one of the most common disorders in South Asia. The Pakistani adult population suffered from cerebral strokes in more than 10% of cases. The TNAP isoform of Alkaline Phosphatase is also found in the brain. It is possible to diagnose cerebral stroke patients based on their serum ALP level. In this study, the objective is to evaluate the level of ALP in patients suffering from cerebral strokes. Methodology: This cross-sectional study was conducted at the Department of Medicine at the LUMHS Jamshoro. A total of 55 patients (26 males &amp; 29 females) with cerebral stroke between the ages of 40-70 years were selected according to the inclusion &amp; exclusion criteria between the ages of 40-70 years. By using the AMP (2-amino, 2-methyl, 1 propanol) method, we were able to estimate the serum level of ALP. Results: In 29.1% of the patients, the mean serum ALP level was 85.13 ± 10.93 U/L, while in 70.9% of the patients, the mean serum ALP level was 231 .42 ± 5.76 U/L. As a result of this study, it can be concluded that approximately 70% of cerebral stroke patients had elevated levels of serum ALP levels, which can be used as a diagnostic tool for cerebral stroke patients. Conclusion: Cerebral stroke patients had elevated serum ALP levels, which are a cheap and easily quantifiable biomarker. Keywords: Cerebral Stroke, Alkaline Phosphatase, TNAP, Isoenzym