Biomarkers in Nonclinical Drug Development

Aulbach, Adam D.; Amuzie, Chidozie

doi:10.1016/b978-0-12-803620-4.00017-7

Cited by 54 publications

(46 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the contrary, no change in AST enzyme levels occurred in either DM group. With hepatocellular damage, the increase in ALT is generally greater than AST, because ALT has a longer half-life and larger fraction bound to mitochondria, which may explain the differences found between ALT and AST levels in our study (Aulbach & Amuzie, 2017).…”

Section: Discussioncontrasting

confidence: 55%

Jabuticaba (Plinia trunciflora(O. Berg) Kausel) improved the lipid profile and immune system and reduced oxidative stress in streptozotocin‐induced diabetic rats

et al. 2020

View full text Add to dashboard Cite

The aim of this study was evaluating the effects of jabuticaba aqueous extract (JPE ‐ 0.5 g/kg) on serum lipid levels, immune system, and oxidative stress parameters of streptozotocin‐induced diabetic rats. Administration of JPE for 30 days, by gavage, was able to reduce serum levels of total cholesterol, non‐high density lipoprotein (HDL) cholesterol, and triglycerides in diabetic rats. The HDL cholesterol levels increased in both diabetic and healthy rats after JPE treatment. Total leukocyte and lymphocyte counts reduced in diabetic rats, and JPE treatment prevented these diabetes mellitus (DM)‐induced changes in the immune system. In addition, the induction of DM also led to dysregulation in the activity of superoxide dismutase and catalase antioxidant enzymes as well as an increase in oxidative stress markers. Treatments with JPE reduced oxidative stress and modulated antioxidant enzyme activities. These data demonstrate the potential of JPE as an adjuvant treatment option for diabetic patients. Practical applications Considering that it is very common to observe dyslipidemia in diabetic patients and that these alterations, combined with the increased oxidative stress levels, also common in these patients, can lead to the development of cardiovascular diseases, JPE would be an alternative treatment adjunct to reduce these risks. In addition, although more studies are needed, JPE has the potential to improve the count of total lymphocytes and leukocytes, which could assist in improving the immune response of these patients, who also commonly have a higher risk of infectious diseases. Thus, JPE could be used by these patients, in combination with conventional treatment, in the form of a nutraceutical rich in phenolic compounds.

show abstract

Section: Discussioncontrasting

confidence: 55%

Jabuticaba (Plinia trunciflora(O. Berg) Kausel) improved the lipid profile and immune system and reduced oxidative stress in streptozotocin‐induced diabetic rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In juvenile female offspring we found increased fibrosis without damage of hepatic lobule, according to elevated ALT and AST levels. These increased concentrations of amino transaminases, which are clinical indicators of liver function [75,76], also in rabbits [77,78], were probably related to histopathological changes in the liver [79]. Generally, ALT level rise is higher than AST level when both are elevated, because of the longer half-life of ALT and the more significant fraction of AST that is bound to the mitochondria [80].…”

Section: Discussionmentioning

confidence: 99%

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

et al. 2021

View full text Add to dashboard Cite

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered.

show abstract

“…Sodium valproate mediated hepatic injury is associated with dose dependent rise in serum liver enzymes. 22 Most notably is the fact that GGT was significantly increased in children on other AEDs (with CBZ as the most prescribed drug in this group) compared to children on VPA group and controls. Gamma glutamyl transferase is more specific than the rest since is an inducible enzyme, the only inducible enzyme in this class of enzymes, buttressing the fact that CBZ is a liver enzyme inducer which can precipitate attacks likely via an increase in catabolism of hydroxymethylbilane synthase and uroporphyrinogen decarboxylase affecting heme synthesis.…”

Section: Discussionmentioning

confidence: 77%

“…Sodium valproate mediated hepatic injury is associated with dose dependent rise in serum liver enzymes. 22…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the plasma AST/ALT ratio could be a better marker of hepatic injury rather than the absolute AST level, with a ratio less than 1 indicating hepatocellular injury. 22 Only 3 of the 18 children with elevated AST levels in group III has an AST/ALT ratio <1, and this raises the possibility of the elevated AST being largely from a nonhepatic source in the cohort. The mean plasma levels of AST did not show any significant elevation in children with epilepsy on treatment with VPA.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Non-Dose-Dependent Changes in Liver Enzyme Levels of Children With Epilepsy on Treatment With Sodium Valproate

2020

View full text Add to dashboard Cite

Background: Sodium valproate (VPA) is considered as the drug of choice for the treatment of generalized epilepsy in children. Sodium Valproate may be hepatotoxic. Aim: To assess the level of derangement of liver enzymes in children with epilepsy on treatment with sodium valproate. Methods: A cohort study. One hundred fifty-three children, comprising 51 with epilepsy on treatment with VPA (group I), 51 with epilepsy on treatment with other antiepileptic drugs (AEDs) but not VPA (group II), and 51 with nonconvulsive disorders (group III) had liver function tests performed for them. Data were analyzed by SPSS version 23.0. Results: There were 85 males and 68 females, aged 6 months to 14 years (median = 7.0 years). There was no significant difference in the mean plasma levels of alanine transaminase (ALT), alkaline phosphatase, and gamma glutamyl transferase across the three groups of children. The mean aspartate transaminase level was significantly higher in children in group III. There was a statistically significant negative correlation between the duration of AED therapy and the mean serum level of AST ( r = −0.266, P = 0.016). The serum ALT level showed a statistically significant positive correlation with the duration of AED therapy ( r = 0.268, P = 0.015). Conclusion: Sodium valproate monotherapy does not appear to be associated with significant hepatotoxicity in children in our cohort.

show abstract

Biomarkers in Nonclinical Drug Development

Cited by 54 publications

References 100 publications

Jabuticaba (Plinia trunciflora(O. Berg) Kausel) improved the lipid profile and immune system and reduced oxidative stress in streptozotocin‐induced diabetic rats

Jabuticaba (Plinia trunciflora(O. Berg) Kausel) improved the lipid profile and immune system and reduced oxidative stress in streptozotocin‐induced diabetic rats

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

Non-Dose-Dependent Changes in Liver Enzyme Levels of Children With Epilepsy on Treatment With Sodium Valproate

Contact Info

Product

Resources

About