Prophylactic and Therapeutic Efficacy of Boric Acid on Lipopolysaccharide-Induced Liver and Kidney Inflammation in Rats.

In our study, we aimed to examine possible prophylactic (P) or therapeutic (T) effects of boric acid (BA) on lipopolysaccharide (LPS) induced liver and kidney damages. Thirty-two rats were divided into four groups as control, LPS, BAP+LPS, and LPS+BAT. BA was given orally to the rats one hour before the intraperitoneal LPS administration in the BAP+LPS group and one hour after the LPS administration in the LPS+BAT group. Malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-6 (IL-6), IL-10, reduced glutathione (GSH), total oxidant and antioxidant status (TOS and TAS), semaphorin-3A (SEMA3A), cytochrome c (CYCS), and caspase-3 (CASP3) parameters were determined by ELISA method to monitor inflammation, oxidative stress, and apoptosis in the liver and kidney tissues of rats. In addition, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine (CREA), C-reactive protein (CRP), gamma glutamyl transferase (GGT), glucose (GLU), sodium (Na), potassium (K), and chlorine (Cl) biochemical parameters were measured in rat serums to monitor liver and kidney functions. Liver and kidney tissues were also examined histopathologically and immunohistochemically. All data were statistically analyzed. Our histological, biochemical, inflammatory, oxidative stress, and apoptotic findings showed that LPS causes serious damage to liver and kidney tissues. Boric acid application brought about significant improvements on the parameters. However, this improvement was seen in the BAP+LPS group, and the results of the LPS+BAT group were insufficient to improve. Our results showed that boric acid administration is effective on severe liver and kidney damage caused by LPS. It has been concluded that prophylactic application is more effective, while therapeutic application is insufficient.

LoxBlock-1 or Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in Ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling.

In this study, the effects of the pretreatment of Curcumin and LoxBlock-1 on liver, pancreas, and cardiac dysfunction following Ischemia-Reperfusion-induced (IR) Acute Kidney Injury (AKI) were investigated through the mechanisms of oxidative stress and ferroptosis. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) parameters in the tissue were analyzed to investigate the oxidative stress occurring in the liver, pancreas, and heart, and Acyl-Coa synthetase long-chain family member (ACSL4). Glutathione peroxidase 4 (GPx4) enzyme levels were also analyzed by ELISA to investigate the effect on ferroptosis. In addition, hematoxylin-eosin staining was performed for histopathological examination of the tissues. As a result of biochemical analyzes, it was observed that oxidative stress parameters increased significantly in the IR group. In addition, while the ACSL4 enzyme level increased in the IR group in all tissues, the GPx4 enzyme level decreased. In the histopathological examination, it was observed that IR caused serious damage to the heart, liver, and pancreas tissues. The present study shows that Curcumin and LoxBlock-1 have a protective effect on the liver, pancreas, and cardiac ferroptosis following the effect on AKI. In addition, Curcumin was found to be more effective than LoxBlock-1 in I/R injury with its antioxidant property.

Oxidative Status and Thiol/Disulfide Homeostasis Are Changed During 75 g Oral Glucose Tolerance Test over a Five-Hour Period.

BACKGROUND: Oral glucose loading may affect oxidative status during oral glucose tolerance test (OGTT). We aimed to investigate how oxidant and antioxidant markers and thiol/disulfide parameters change during OGTT. METHODS: OGTT was performed to 42 volunteers who were considered risk of type 2 diabetes and were divided into three groups (normoglycemic, prediabetes, diabetes) according glucose levels during OGTT. Glucose, insulin, c-peptide, total antioxidant status (TAS), total oxidant status (TOS), total thiol and native thiol were investigated with auto-anaylzer for five-hours period. RESULTS: Decrease of TAS and increase of TOS levels began with the increase in glucose and insulin levels. The increase of TAS started at third hour and reached the highest levels at fifth hour. OSI levels were higher at fourth hour than fasting and first hours in normoglycemic and diabetes groups. In the prediabetic group, TAS were higher than the other groups, TOS peak was at the second hour (p < 0.05). Native thiol and total thiol levels showed variable course during OGTT, both parameters increased at the end of the process (p < 0.05). Disulfide levels showed an increase trend but it was not statistically different in normoglycemic and diabetes groups. In prediabetes group, second hour disulfide level was lower than fasting state and disulfide was significantly increased at third, fourth and fifth hours and fifth hour disulfide level was also higher than fasting. CONCLUSION: Oxidative stress parameters and thiol/disulfide balance were found to deteriorate within five-hours after glucose loading in all groups. These results indicates that oxidative stress occurs during OGTT.

Probiotics ameliorates LPS induced neuroinflammation injury on Aß 1-42, APP, γ-ß secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes.

The gut microbiota influences brain development and functioning through the gut-brain axis. This is first study regulate maternal gut microbiota and fetal neurodevelopment processes by using probiotics such as Bifidobacterium bifidum (BIF) and Lactobacillus salivarius (LAC) in the prenatal period. In this study, Wistar Albino female rats were divided into five groups; Control, lipopolysaccharide (LPS, 100 µg/kg), LPS + LAC, LPS + BIF and LPS + LAC + BIF (4 × 109 ml CFU). Maternal rats were given probiotics for 21 days. Inflammation was induced by lipopolysaccharide (LPS), on the 17th day of pregnancy. After birth, the brain tissues of the maternal and neonatal rats were removed and their blood was collected. Fecal calprotectin levels of pregnant rats were measured as an important biomarker in determining intestinal flora disruption. Calprotectin levels were high in LPS group (p < 0.05). Aß 1-42, APP, γ secretase and ß- secretase levels were higher in both maternal and neonatal LPS groups (p < 0.05). These levels were statistically decreased in the probiotic groups compared to the LPS group, as demonstrated in both biochemical and histological analyzes (p < 0.05). While BDNF mRNA expression decreased in LPS groups, APP level increased in the same group. The difference between groups in mRNA expressions in the neonatal brain tissues was similar to maternal brain tissues. What's more, BDNF/actin and APP/actin rates were proven by western blot and the damage caused by neuroinflammation in the brain tissue and the preservation of the intestinal microbiota were visualized histopathologically on the morphological structures in all groups. It will shed light on new therapeutic strategies for the impact of the use of probiotics on the neurodevelopmental processes of the neonatal against LPS-induced inflammatory responses and impaired gut microbiota in the prenatal period.

The effects of N-acetylcysteine on experimentally created l-asparaginase-induced liver and pancreatic damage in rats.

In this study, oxidative stress marker (malondialdehyde, MDA) and antioxidant enzymes (glutathione (GSH), catalase (CAT)) levels in the liver and pancreas tissue and the histopathological effects of N-acetylcysteine (NAC) were investigated in l-asparaginase (l-ASP) induced liver and pancreatic damage in rats. Forty male albino rats were divided into four groups. The control group was intraperitoneally injected physiological saline (0.02 mL/g); NAC group was injected NAC (200 mg/kg, five days); l-ASP group was injected single-dose l-ASP (10,000 U/kg), and l-ASP + NAC group was injected NAC for five days following single-dose l-ASP (10,000 U/kg). The surgical operation was performed on all animals on the fifth day. There was no difference between the groups regarding tissue MDA, GSH, and CAT levels (p>.05, for all). In the group receiving NAC after l-ASP, there was a significant improvement in the liver and pancreas damage score than the l-ASP group. NAC was effective in reducing organ damage caused by l-ASP.

Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21.

Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria that produces endotoxemia, which may cause septic shock. Metformin (MET) is a widely used hypoglycemic drug that exhibits anti-inflammatory properties. Fibroblast growth factor 21 (FGF21) is an endocrine polypeptide that affects glucose and lipid metabolism, and also possesses anti-inflammatory properties. We investigated the effects of MET and FGF21 on inflammation due to LPS induced endotoxemia in male rats. Animals were divided into five groups: control, LPS, pre-MET LPS, LPS + 1 h MET and LPS + 3 h MET. Serum levels of alanine aminotransferase, aspartate aminotransferase, FGF2, interleukin-10 and tumor necrosis factor alpha were measured. Malondialdehyde, myeloperoxidase and FGF21 levels were measured in liver tissue samples. Histopathology of all groups was assessed using hematoxylin and eosin stained sections. LPS caused severe inflammatory liver damage. MET exhibited a partially protective effect and reduced inflammation significantly. FGF21 is produced in the liver following inflammation and MET may increase its production.

Conivaptan and Boric Acid Treatments in Acute Kidney Injury: Is This Combination Effective and Safe?

Acute kidney injury is still a worldwide clinic problem that affects kidney function and associated with high mortality risk. Unfortunately, approximately 1.7 million people are thought to die from acute kidney injury each year. Boron element is defined as an "essential trace element" for plants and thought to have a widespread role in living organisms. Boric acid, which is one of the important forms of boron, has been extensively discussed for both medicinal and nonmedicinal purposes. However, there is a lack of data in the literature to examine the relationship between boric acid and antidiuretic hormone (ADH) antagonism in kidney injury. Thus, we aimed to investigate the effects of conivaptan as an ADH antagonist and boric acid as an antioxidant agent on the post-ischemic renal injury process. In this study, the unilateral ischemia-reperfusion (I/R) injury rat model with contralateral nephrectomy was performed and blood/kidney tissue samples were taken at 6th hours of reperfusion. The effects of 10 mg/mL/kg conivaptan and 50 mg/kg boric acid were examined with the help of some biochemical and histological analyses. We observed that conivaptan generally alleviated the destructive effects of I/R and has therapeutic effects. Also of note is that conivaptan and boric acid combination tended to show negative effects on kidney function, considering the highest BUN (78.46 ± 3.88 mg/dL) and creatinine levels (1.561 ± 0.1018 mg/dL), suggesting possibly drug-drug interaction. Although it has reported that conivaptan can interact with other active substances, no experimental/clinical data on the possible interaction with boric acid have reported so far.

Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta (1-42).

Synaptosomes are used as an ex vivo model in the investigation of neuronal transmission and neurodegenerative processes. In this study, we aimed to determine the protective effects of boric acid (BA) and curcumin, which have antioxidant and anti-inflammatory properties, on Aß1-42 induced neurodegenerative damage. Synaptosomes obtained from the rat cerebral cortex were divided into five groups: control, 10 µM Aß1-42, 10 µM Aß1-42 + 25 mM BA, 10 µM Aß1-42 + 10 µM curcumin, and 10 µM Aß1-42 + 25 mM BA+10 µM curcumin. Synaptosomes treated with Aß1-42 caused a significant decline in synaptophysin levels and increase in malondialdehyde (MDA) levels, acetylcholinesterase (AChE) activities, DNA fragmentation values, and nitric oxide (NO) levels compared with the control group (P < 0.01). Synaptosomes treated with BA showed a significant reduction in MDA and NO levels against Aß1-42 exposure (P < 0.01). In addition, curcumin treatment has been found to cause a significant reduction in AChE activities and MDA levels in synaptosomes (P < 0.05). Co-administration of BA and curcumin on synaptosomes exposed to Aß1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities. Curcumin and BA + curcumin combination showed an enhancement in synaptophysin levels of Aß1-42-induced synaptosomes (P < 0.01). The results showed that BA and curcumin had protective effects on rat brain synaptosomes against Aß1-42 exposure. BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of Aß1-42 exposed.

Evaluation of Total Antioxidant Capacity and Total Oxidant Status of Preterm and Term Breast Milk during the Course of Lactation and within a Nursing Session.

OBJECTIVE: Breast milk (BM) contains antioxidant molecules which may offer protection against oxidative stress (OS). We aim to investigate oxidant-antioxidant balance in preterm BM during the course of lactation and within a nursing session. STUDY DESIGN: Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in colostrum, transitional, and mature BM samples of preterm infants born earlier than 34th week of pregnancy and healthy term infants. Oxidative stress index (OSI) was calculated. Foremilk and hindmilk samples were collected separately. RESULTS: In colostrum and transitional milk, TAC (p < 0.001 and p = 0.001, respectively) and TOS (p = 0.005 and p < 0.001, respectively) were lower in preterm BM compared with term BM. OSI was also lower in preterm BM, but it was statistically significant only in transitional milk (p < 0.001). TAC was highest in colostrum and decreased through the course of lactation. However, the decrease in TAC was not statistically significant in preterm BM. Lowest values of TOS and OSI were observed in colostrum. In transitional term BM, hindmilk had a better oxidant-antioxidant profile as indicated by lower TOS and OSI. CONCLUSION: Oxidant-antioxidant balance is preserved in BM in every stage of lactation. Preterm BM has lower OSI which may offer benefits to preterm newborn against OS.

Comparison of measured and calculated osmolality levels.

BACKGROUND: Serum osmolality levels are measured to determine acid-base and electrolyte imbalance in serum. In cases where measurement is not possible, the serum osmolality value can be calculated by various calculation methods. In this study, we compared the Worthley osmolality calculation method which is used most frequently mentioned in literature and the measurements made with vapor pressure osmometer used in our laboratory. We compared whether there was a difference between the results obtained by measurement and calculation method in different age groups. METHODS: 221 serum samples of patients who were admitted to the Eskisehir Osmangazi University Hospital Biochemistry Laboratory between December 2016 and May 2018 were included in this study. Glucose, blood urea nitrogen and sodium values were recorded to determine the calculated osmolality values of the patients. RESULTS: There was a statistically significant difference between the measured osmolality values and the calculated osmolality values of the patients (p < 0.001). When compared according to age groups, there was a significant difference between calculated osmolality values (p = 0.006), but there was no difference in measured osmolality values (p = 0.787) in different age groups. It has been observed that this difference in the calculated osmolality values between the age groups is derived from the adult group (18-65, p < 0.001). CONCLUSION: Our results showed that it is not reliable to calculate serum osmolality values, especially in the adult age group. According to our results the calculated osmolality values are higher than our measured osmolality values.

Insulin resistance and pancreatic ß cell dysfunction are associated with thyroid hormone functions: A cross-sectional hospital-based study in Turkey.

BACKGROUND AND AIMS: The prevalence of thyroid disease in diabetic patients is significantly higher than the general population. This indicates a possible interaction between thyroid functions and insulin sensitivity. This study aimed to investigate the relationship between insulin resistance (IR), pancreatic ß cell function, and thyroid function tests. METHODS: This cross-sectional study was conducted with adults who applied to Eskisehir Osmangazi University Hospital for general control. Fasting insulin, glucose, TSH, fT3, and fT4 levels in the serum of 1340 adult (18-60 aged) patients without any chronic diseases were examined retrospectively. The fT3/fT4 ratio, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and HOMA-ß values were calculated. The correlation between HOMA-IR and HOMA-ß values with thyroid function tests and differences between hormone levels of patients with and without IR were evaluated. RESULTS: There was a positive correlation between HOMA-IR and TSH, negative with fT4. Also, a positive correlation between HOMA-ß and fT3, negative correlation with fT4 were observed. In the IR group, fT3 levels were found significantly higher and fT4 levels were significantly lower. TSH levels were higher in the IR group but not statistically significant. The fT3/fT4 ratio was found significantly higher in the IR group and was correlated positively with both HOMA-IR and HOMA-ß. CONCLUSION: Our results revealed that thyroid dysfunction prevalence is quite high in adults who have not yet been diagnosed with diabetes but have insulin resistance and the onset of pancreatic ß cell dysfunction.