Serum ALP Research Articles

In vivo toxicological assessment of silver nanoparticle in edible fish, Oreochromis mossambicus.

Silver nanoparticles are the extensively utilized among all nanoparticles due to their antibacterial and wound healing properties making them highly suitable for medical and pharmaceutical applications. The field of nanoparticle toxicity is an emerging field and the present study aims to assess the biochemical, hematological and genotoxicity in Oreochromis mossambicus exposed to different concentrations of silver nanoparticles for 7 and 14days. Silver nanoparticles were synthesized by reduction of silver nitrate using trisodium citrate and was characterized using X-ray diffraction, SEM, HRTEM and DLS. Hematological parameters like RBC, WBC, Hb, HCT and MCV and for biochemical analysis, antioxidant enzymes SOD, CAT and GPX and serum enzymes AST, ALT, ACP, ALP and LDH were analyzed. Genotoxicity was studied using comet assay. Results obtained showed decrease in erythrocytes, HCT, Hb and MCV while an increase was noted in WBC on day 7 and 14. The antioxidant enzymes SOD, CAT and GPx showed a decrease and the lipid peroxidation product MDA was elevated. The serum enzymes AST, ALT, ACP ALP and LDH showed an increased activity when compared to control. DNA damage was evident by an increase in % TDNA. The results indicate hematological, biochemical and genotoxicity of silver nanoparticles that might be mediated through ROS generation in O. mossambicus.

Behavioral, Maternal and Neurological Effects of Monosodium Glutamate on Pregnant Female Rats During Early and Late Gestation

Seventy-five adult Wistar Albino rats were used in this experiment to detect the effect of MSG on fetus morphology, and pregnant rats’ behavioral, biochemecal, and neurological parameters. They were housed under standard laboratory conditions in plastic cages in a quiet environment with free access to food and water. They were randomly assigned into 4 groups of three replicates for each. Group (1) control, received normal saline. Groups (2, 3, and 4) received daily MSG orally at a dose of 1, 3 and 6 mg/kg respectively for a period of 20 days. There was a reduction in the mean number of fetuses /dam, an altered distribution of implantation, reduction in fetuses’ weight & length, besides some fetuses revealed morphological anomalies and skeletal defects at the 19th day of gestation. In addition, there was a decrease in the number of entrance and spontaneous alternations, increase in line crossing and rearing behaviors, elevation in serum ALT, AlP and creatinine, decrease in serum progesterone, increase in dopamine and glutamate levels (ng/mL) in brain tissues of MSG treated pregnant rats. So that, this study suggests that to diminish MSG in foods during pregnancy to to stay away from harmful effects on pregnant females behavior, brain tissue, and safe fetuses from deformity.

Ameliorative potential role of Rosmarinus officinalis extract on toxicity induced by etoposide in male albino rats.

The present work was showed to assess the effect of administration of rosemary extract on etoposide-induced toxicity, injury and proliferation in male rats were investigated. Forty male albino rats were arranged into four equal groups. 1st group, control; 2nd group, etoposide; 3rd group, co-treated rosemary & etoposide; 4th group, rosemary alone. In comparison to the control group, etoposide administration resulted in a significant increase in serum ALT, AST, ALP, total bilirubin, total protein, and gamma GT. In contrast; a significant decrease in albumin level in etoposide group as compared to G1. G3 revealed a significant decrease in AST, ALT, ALP, total protein and total bilirubin levels and a significant rise in albumin level when compared with G2. Serum levels of urea, creatinine, potassium ions, and chloride ions significantly increased; while sodium ions were significantly decreased in G2 when compared with G1. Also, there was an increase of MDA level for etoposide treated group with corresponding control rats. However, there was a remarkable significant decrease in SOD, GPX and CAT levels in G2 as compared to G1. There was a significant increase in serum hydrogen peroxide (H2O2) and Nitric oxide (NO) levels in group treated with etoposide when compared to control group. It was noticeable that administrated by rosemary alone either with etoposide had not any effect on the levels of H2O2 and Nitric oxide. Serum level of T3 and T4 was significantly increased in etoposide-administered rats in comparison with G1. The administration of rosemary, either alone or with etoposide, increased the serum levels of T3 and T4 significantly when compared to control rats. The gene expression analysis showed significant downregulation of hepatic SOD and GPx in (G2) when compared with (G1). The treatment with rosemary extract produced significant upregulation of the antioxidant enzymes mRNA SOD and GPx. MDA gene was increased in (G2) when contrasted with (G1). Treatment of the etoposide- induced rats with rosemary extract delivered significant decrease in MDA gene expression when compared with etoposide group. Rats treated with etoposide showed significant decline in hepatic Nrf2 protein expression, when compared with G1. While, supplementation of Etoposide- administered rats with the rosemary produced a significant elevation in hepatic Nrf2 protein levels. Additionally, the liver histological structure displayed noticeable degeneration and cellular infiltration in liver cells. It is possible to infer that rosemary has a potential role and that it should be researched as a natural component for etoposide-induced toxicity protection.

Preclinical Evaluation of Nerolidol’s Hepatoprotective and Nephroprotective Potential

Background: Due to the potential negative effects of artificial food additives on health and the recent surge in consumer awareness of the issue, natural goods are becoming more and more popular in diets. Objective: The main objective of the current study is the evaluation of the protective effect and antioxidant role of Nerolidol against alloxan-induced oxidative stress, hepatotoxicity, and nephrotoxicity. Method: The present experiment was designed as Group I (control), Group II (Alloxan monohydrate, 120 mg/kg i.p), Group III (Ascorbic acid 250 mg/kg p.o), Group IV (Nerolidol 100 mg/kg p.o), Group V (Nerolidol 200 mg/kg p.o), Group VI (Nerolidol 300 mg/kg p.o). Alloxan was given to all groups excluding control group in order to induce hepatorenal toxicity. The groups III, IV, V and VI received the Standard Ascorbic acid and Nerolidol after 72 hrs. of alloxan administration for consecutive 14 days. The protective roles and antioxidant activity of Nerolidol against Alloxan induced oxidative stress and hepatorenal toxicity were evaluated by histopathological changes, measuring hepatic and renal damage biomarkers, antioxidant enzyme levels and malondialdehyde (MDA) parameters in the liver and kidney tissues of rats. Result and Conclusion: The biochemical analysis showed a decrease in serum AST, ALT, ALP, and LDH enzymes, total protein, creatinine, bilirubin, and urea in group III and test groups compared to that of group II. Nerolidol also restored the Alloxan-induced MDA and antioxidant enzyme level to control. Hepatorenal protection of Nerolidol was confirmed by almost normal histological findings in test groups.

Akut pankreatitli hastalarda akut pankreatik ve peripankreatik sıvı gelişiminde prediktif faktörler

Aims: Acute fluid collections after acute pancreatitis carries risk of serious complications as infected pseudocyst and Wall off Necrose development. Hence, it is important to predict the development of acute fluid collections for treatment and management of acute pancreatitis. In this study, it is aimed to investigate predictive factors for development of acute fluid collections in patients with acute pancreatitis. 
 Methods: Total of 438 patients diagnosed with acute pancreatitis were screened. According to the Revised Atlanta Classification fluid development after acute pancreatitis was determined and the relationship between fluid development and the hematological/biochemical parameters of the patients at the time of admission was investigated. The best cut-off point of laboratory measurements for fluid development was determined by ROC analysis and the factors that may be most decisive in distinguishing between the patients with and without fluid development were determined by multivariate forward stepwise logistic regression analysis.
 Results: It is found that developing acute fluid collections after acute pancreatitis was higher in patients with younger age and male gender. Also the risk of developing acute fluid collections after acute pancreatitis was found to be 6.2 times higher in patients with CRP/Albumin ratio greater than 1.09; 2.5 times higher in patients with ALP below 199.5 U/L; 1.9 times higher in patients with WBC greater than 11,6 ×10⁹/L and 1.5 times higher in patients with PLR above 197.1. Also the risk of developing acute necrotic collections after acute pancreatitis was 3 times higher in patients with serum calcium level below 8,6 mg/dl.
 Conclusion: It has been determined that, presence of high CRP/albumin ratio, high NLR and low serum ALP level can be used as an indicator in predicting acute pancreatic and peripancreatic fluid development.

Resveratrol Administration Ameliorates Hepatotoxicity in Mercuric Chloride-‎Induced Liver Injury in Rats

Mercuric chloride (HgCl2) pollution and poisoning has been a worldwide health ‎concern for decades, especially after the industrial revolutions. The aim of this study ‎was to investigate the role of resveratrol in reversing the deleterious effects of ‎HgCl2 exposure to resume the normal functions of hepatocyte. To achieve the study, ‎mature Sprague Dawley rats were assigned to five groups. Negative control group ‎‎(C) kept without any treatment; vehicle-treated group (D) received dimethyl ‎sulfoxide (DMSO); resveratrol-treated group (R), received 100 mg/kg of resveratrol; ‎HgCl2-intoxicated group (HD), received i.p. injection of HgCl2 at a dose of 1 mg/kg ‎for 30 consecutive days along to oral gavage of DMSO; and finally HgCl2-‎intoxicated group treated with resveratrol (HR) as same treatment strategy of R-‎group. At the endpoint of the experiment, blood samples were collected for ‎biochemical liver function tests along with serum concentrations of ‎malondialdehyde (MDA), glutathione (GSH), body weight, as well as ‎histopathological investigation was done too. Study results revealed a significant ‎‎(P<0.05) elevation in serum AST, ALP, GGT, and MDA in HD group in comparison ‎with HR group. However, resveratrol treatment has led to a significant (P<0.05) ‎increase in serum levels of GSH in HR group in comparison with the HD group. ‎Histopathological sections showed vacuolar degeneration in HD hepatocytes while ‎resveratrol treatment protected the hepatocytes against the chemical injury. ‎Altogether, It is concluded that resveratrol administration has the ability to increase ‎the resistance of liver against the HgCl2-induced hepatotoxicity via increase the ‎antioxidant yields such as GSH resulted in reduction of hepatocellular texture ‎damage.

Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = -0.187, p = 0.045) and log-ANGPTL3 (r = -0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.

DOT1L decelerates the development of osteoporosis by inhibiting SRSF1 transcriptional activity via microRNA-181-mediated KAT2B inhibition

ObjectiveOur study explored the function of DOT1L in osteoporosis (OP) via the microRNA (miR)-181/KAT2B/SRSF1 axis. MethodsOsteoclast (OC) number was evaluated via TRAP staining, and serum CTXI, PINP, and ALP contents were tested by ELISA. Following identification of bone marrow mesenchymal stem cells (BMSCs), OC differentiation was induced by M-CSF and RANKL, followed by the detection of OC differentiation and the expression of bone resorption-related genes, DOT1L, miR-181, KAT2B, and SRSF1. ResultsOverexpressed DOT1L or miR-181 stimulated calcified nodule formation and increased alkaline phosphatase activity and osteogenic marker gene expression. KAT2B knockdown enhanced the osteogenic differentiation of BMSCs by reducing SRSF1 acetylation. The enhancement of OC differentiation induced by overexpressed SRSF1 was inhibited by simultaneous DOT1L or miR-181 overexpression. DOT1L suppressed OP development in vivo via the miR-181/KAT2B/SRSF1 axis. ConclusionDOT1L overexpression slowed down bone loss and promoted bone formation via the miR-181/KAT2B/SRSF1 axis, thereby alleviating OP development.

Dietary Theobroma cocao Prevents Hepatotoxicity Secondary to Myocardial Injury

Dietary products like cocoa with high flavonoids may play a role to boost the integrity of the liver against insults resulting from myocardial injury. Twenty-four male Wistar rats, divided into four groups of 6 rats were used for the study. Group 1 was control and received 0.9% normal saline via oral gavage. Group 2 was the acute myocardial injury group, and received two doses of subcutaneous injection of isoproterenol (100 mg/kg body weight) at an interval of 24 hours between doses. Group 3 was administered Theobroma cacao (100 mg/kg body weight orally) only for 2 weeks. Group 4 was pretreated with Theobroma cacao for 2 weeks and then followed by injection of isoproterenol (100 mg/kg body weight) on day 15 and 16. At the end of the experimental period, the rats were euthanized and serum collected for laboratory investigations of lactate dehydrogenase, troponin, alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Administration of isoproterenol resulted in a significant (p&lt;0.001) elevation in the serum concentrations of the cardiac biomarkers, troponins and LDH when compared with the control group. Pretreatment with Theobroma cacao before myocardial infarction caused a significant (p&lt;0.01) reduction in the concentrations of LDH and troponins with values similar to the control group. The serum liver enzymes AST, ALT, and ALP levels were also significantly (p&lt;0.01) but were reversed in the Theobroma cacao cocoa treatment groups. It is concluded that Theobroma cacao prevents hepatic and heart damage thus providing a support for the prophylactic use of dietary Theobroma cacao against hepatotoxicity.

Evaluation of Total and Lipid-Bound Sialic Acids, Trace and Macro Elements, and Some Biochemical Parameters in Dogs with Babesiosis

The present study was designed to investigate the changes at the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), trace and macroelements, and some biochemical parameters in dogs naturally infected with babesiosis. While babesiosis group consisted of seven dogs which were diagnosed with babesiosis clinically and parasitologically (ELISA), control group consisted of seven healthy dogs. Serum TSA and LSA levels in blood samples were measured spectrophotometrically by Sydow and Katapodis methods, respectively. Some biochemical parameters and macroelement measurements were performed using a modular autoanalyzer device. Trace mineral measurements were performed by ICP-MS technique. Compared to the healthy group, dogs with babesiosis had considerably higher TSA and LSA levels. Serum AST, ALP, LDH and CK enzyme activities and CRP, glucose, globulin, total bilirubin, urea, uric acid, creatinine and BUN levels of the babesiosis group significantly increased, while total protein level significantly decreased. The changes in ALT enzyme activity and triglyceride, cholesterol, HDL, LDL, HDL-CDL and ferritin levels were not statistically significant. Zinc, copper, magnesium, sodium, and potassium levels of the babesiosis group decreased significantly, while iron and chlorine levels increased significantly (p

Role of serum alkaline phosphatase as a potential biomarker of severity and prognosis in intracerebral hemorrhage

ObjectivesAlkaline phosphatase (ALP) catalyzes the hydrolysis of pyrophosphate and facilitates vascular calcification. We aimed at investigating serum ALP levels in intracerebral hemorrhage (ICH) patients and ascertaining its relationship to severity and prognosis. MethodsSerum ALP levels from 148 patients and 148 healthy controls were detected. Glasgow coma scale (GCS) score and hematoma volume at admission were recorded to evaluate hemorrhagic severity. Modified Rankin Scale (mRS) score > 2 at 90 days after onset was judged as a poor prognosis. ResultsSerum ALP levels in patients with ICH were substantially elevated compared with healthy controls, and were significantly related to hematoma volume and GCS score. Serum ALP levels significantly distinguished ICH patients at risk for unfavorable prognosis. Serum ALP levels > 78.5 U/L in ICH patients may indicated a unfavorable prognosis with 69.1 % sensitivity and 83.6 % specificity, and served as an independent predictor for unfavorable prognosis. ConlusionsElevated serum ALP levels were intimately connected with increased severity and 90-day unfavorable prognosis in patients with ICH. Serum ALP could be a potential biomarker for severity and prognosis of ICH.

Safety and risk assessment of methanol extract of Ocimum gratissimum leaf on Wistar rats

Methanol extract of Ocimum gratissimum was investigated for its effects on Wistar rats using some kidney and liver functional indices as ‘markers’. Twenty- eight (28) albino rats weighing 180-200 g was randomly assigned into four groups (A-D) of seven animals each. Animals in groups B-D was orally administered on daily basis with 0.5 ml of the extract corresponding to 50,100 and 200 mg/kg body weight of the extract respectively for 14 days while those in the control group received orally 0.5 ml of distilled water. Rats in all the groups were sacrificed 24 hours after the completion of their respective doses and serum, liver and kidney tissue samples were collected for biochemical parameters. The extract significantly (p&lt;0.05) decreased serum, liver and kidney ALP, AST and ALT. The extract also significantly (p&lt;0.05) reduced serum urea, uric acid and creatinine. Contrastingly, the extract significantly (p &lt; 0.05) increase in serum albumin, globulin and total protein respectively when compared with the normal control at 50, 100 and 200 mg/kg body weight respectively. The effect of administration of the extract on serum Na+, K+, Cl- and HCO3- ions shows a significant (p&lt;0.05) decrease when compared with the normal control with the exception of an increase in K+ ion concentration at 200 mg/kg bwt when compared with the normal control. The biochemical alterations from this result suggest that the extract of Ocimum gratissimum may induce hyponatremia and hypokalaemia at high dosage possibly by altering the Na + /H – exchanger with aldosterone without causing assault or injury to the hepatic, nephrotic and /or tubular function.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

Evaluating the hepatotoxic versus the nephrotoxic role of iron oxide nanoparticles: One step forward into the dose-dependent oxidative effects

The present study has been designed to detect the dose-dependent effect of iron oxide nanoparticles (IONPs) on the liver and kidney of rats by evaluating three different doses 30, 300, 1000 mg/kg/day IONPs for 28 days. Forty rats were divided into four groups; I (control), II (low dose), III (medium dose) and IV (high dose).There also was a statistically-significant elevation in the serum levels of hepatic enzymes; AST and ALT in medium & high dose. The elevation of serum ALP, on the other hand, was significant in all IONPs doses.There was significant elevation in the levels of urea creatinine, and MDA in the medium and high doses of IONPs. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed significant decrease in the high dose only compared to the control group.The serum iron levels increased in a dose-dependent manner in the IONPs-treated groups with highly significant increase in the moderate and high dose groups.On comparing the effect of different doses of IONPs between the liver and kidney, the high dose revealed statistically significant difference (p < 0.05) in the area percent of collagen deposition (54.4 ± 3.9 versus 6.1 ± 2.6) and alpha smooth muscle actin (α-SMA) reaction (7.7 ± 1.5 versus 17.8 ± 4.3) in the liver relative to the kidney. The medium and high doses revealed statistically significant difference in optical density of Periodic acid Schiff (PAS) reaction (45 ± 3.4 versus 50.3 ± 1.8 in the medium dose, and 38.9 ± 6 versus 63 ± 3 in the high dose) and area percent of inducible nitric oxide synthase (iNOS) reaction (12.98 ± 2.7 versus 3.5 ± 0.5 in the medium dose, and 27.91 ± 1.5 versus 7.7 ± 0.6 in the high dose) in the liver relative to the kidney.

Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect

Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome-proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. Methods: One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. Results: Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not significantly change, but M2-BPGi, an index of fibrosis, significantly decreased. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions: As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Serum Bile Acids Concentrations and Liver Enzyme Activities after Low-Dose Trilostane in Dogs with Hyperadrenocorticism.

Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1-3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels.

Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease

BackgroundHypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis. Clinical reportA 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: <115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 μg/L; reference value: 5.7–32.9 μg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 μg/L respectively). ConclusionsWe demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.

Morroniside Inhibits Inflammatory Bone Loss through the TRAF6-Mediated NF-κB/MAPK Signalling Pathway.

Osteoporosis is a chronic inflammatory disease that severely affects quality of life. Cornus officinalis is a Chinese herbal medicine with various bioactive ingredients, among which morroniside is its signature ingredient. Although anti-bone resorption drugs are the main treatment for bone loss, promoting bone anabolism is more suitable for increasing bone mass. Therefore, identifying changes in bone formation induced by morroniside may be conducive to developing effective intervention methods. In this study, morroniside was found to promote the osteogenic differentiation of bone marrow stem cells (BMSCs) and inhibit inflammation-induced bone loss in an in vivo mouse model of inflammatory bone loss. Morroniside enhanced bone density and bone microstructure, and inhibited the expression of IL6, IL1β, and ALP in serum (p < 0.05). Furthermore, in in vitro experiments, BMSCs exposed to 0-256 μM morroniside did not show cytotoxicity. Morroniside inhibited the expression of IL6 and IL1β and promoted the expression of the osteogenic transcription factors Runx2 and OCN. Furthermore, morroniside promoted osteocalcin and Runx2 expression and inhibited TRAF6-mediated NF-κB and MAPK signaling, as well as osteoblast growth and NF-κB nuclear transposition. Thus, morroniside promoted osteogenic differentiation of BMSCs, slowed the occurrence of the inflammatory response, and inhibited bone loss in mice with inflammatory bone loss.

THU436 Small Intestinal Bacterial Overgrowth Causing Osteoporosis In An Adult Male

Abstract Disclosure: S. Aziz: None. S.A. Patrick: None. V. Mupparaju: None. S. Kode: None. Background: Small intestinal bacterial overgrowth (SIBO) is a disease caused by intestinal dysbacteriosis which can lead to nutrients malabsorption and chronic metabolic acidosis which affect bones health and cause osteoporosis. Clinical Case: A 45-year-old man with medical issues of GERD presents to the endocrinology clinic in 02/2022 for evaluation of incidental finding of T5 vertebral fracture noted in the chest x-ray done for evaluation of chest tightness. During the clinic visit the patient reported chronic bloating and gassiness. Denied symptoms suggestive of eating disorders, chronic fatigue, decreased libido, recurrent fractures, elastic skin, hypermobile joints or joint dislocation, and steroid use. Patient is married and has two biological children. He drinks alcohol socially and denied tobacco use. Patient was taking cholecalciferol 1000 IU daily at home. His weight is 64 kg with a BMI of 21 kg/m2. Physical examination did not reveal any abnormality. Bone mineral density showed the worst Z-score of -2.3 in his spine. Workup for osteoporosis included 24-hour urine calcium, CBC, CMP (including serum calcium, phosphorus, electrolytes, ALP, and creatinine), PTH, TSH, free plasma cortisol, ACTH, morning total testosterone, 25-hydroxyvitamin D level, SPEP, UPEP, celiac disease screening tests (tissue transglutaminase IgA and tTG IgG), IGF-1 and HbA1c were all within normal limits. The patient was started on alendronate 70 mg once weekly and was referred to a local gastroenterologist for further evaluation of his GI symptoms; he subsequently was diagnosed with SIBO which is the most likely cause for his osteoporosis. Conclusion: SIBO is a disease caused by intestinal dysbacteriosis, which is caused by replacement of physiologic bacteria by pathogenic bacteria from the large intestine leading to maldigestion and malabsorption of nutrients including fat, carbohydrates and protein leading to vitamins deficiencies and metabolic acidosis. Due to impaired absorption of nutrients it can cause systemic complications including osteoporosis. Fat malabsorption can lead to deficiencies of fat-soluble vitamins A, D, K and E. SIBO can also result in protein-losing enteropathy. The state of chronic metabolic acidosis caused by SIBO increases alkali mobilization from the bone and induces dissolution of the bone thus promotes the development of osteoporosis. Gastrointestinal diseases including SIBO should be considered in cases of osteoporosis of unknown origin. Presentation: Thursday, June 15, 2023

THU458 Demineralization Zebras: A Rare Case Of Hypophosphatasia In An Adult Presenting With Osteopenia

Abstract Disclosure: B.P. Ramchandani: None. A. Khan: None. H. Aftab: None. Introduction: Hypophosphatasia (HPP) is a rare genetic bone disease with only 500-600 cases reported in the United States. It is characterized by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, leading to impaired bone mineralization. HPP presenting in the perinatal period is fatal. During infancy, rachitic deformities develop by age 6 months. Children present with early loss of deciduous teeth and delayed milestones while in adulthood, HPP is characterized by recurrent fractures, osteoporosis, and muscle weakness. We describe a case of HPP diagnosed in a patient after low ALP was discovered on laboratory testing. Case: A 69-year-old female presented for the evaluation of osteopenia. She had a history of fracture of the right knee as well as fracture of the base of the right 5th metatarsal and lateral aspect cuboid, which healed well with conservative management. Dental history was significant for 5 implants over the last 15 years. She was on vitamin D supplements and had also taken risedronate for osteopenia for 14 years which was discontinued at her first visit with us. Family history was significant for osteoporosis in her mother. Initial lab studies were significant for an ALP of 29 U/L (ref range 39-113 U/L), phosphate of 4.9 mg/d (ref range 2.4-4.8 mg/dl), pyridoxal 5’-phosphate level (vitamin B6) of 308 nmol/L (ref range 20-125 nmol/l), a vitamin D 25-OH level of 20 ng/mL (ref range &amp;gt;30 ng/ml) and PTH of 49 pg/dl (ref range 15-88 pg/ml). Repeat lab testing done 6 months after stopping risedronate showed consistent similar results with an ALP of 32 U/L, phosphate level of 5.1 mg/dl, vitamin B6 level of 349 nmol/L, and vitamin D 25OH level of 26 ng/mL. Bone density scan revealed a lumbar spine BMD of 1.503 g/cm2 (T-score 2.5) and a mean total hip BMD of -0.3 consistent with osteoporosis of spine and osteopenia of hip. Genetic testing and counseling were offered to the patient, however she declined. Discussion: Our patient presented with recurrent fractures and loss of dentition requiring multiple dental implants in the background of osteopenia. Given persistently low serum ALP and elevated serum vitamin B6 levels her presentation suggested a diagnosis of HPP. Management includes supportive treatment with prompt treatment of fractures, and routine dental care. Although there is no approved medication for adults, enzyme therapy replacement with asfotase-alfa (a recombinant human ALP) is FDA-approved for pediatric-onset HPP which improves bone mineralization and muscle strength, however discontinuation of therapy leads to reappearance of bone hypomineralization. Once the diagnosis is made, genetic testing and counseling should be offered to prevent complications in future pregnancies. Presentation: Thursday, June 15, 2023