Most cited article - PubMed ID 11829314
The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas
Butyrylcholinesterase (BChE) has recently been associated with metabolic imbalance. A correlation between plasma activity and lipid and glucose metabolism has been reported in animal models and human patients. Here, we investigated plasma BChE activity in a rat model of comorbid hypertension and type 1 diabetes mellitus (DM) induced by a single injection of streptozotocin (STZ, 55 mg/kg) in male spontaneously hypertensive rats (SHR) (SHR+DM). The SHR+DM animals exhibit the main characteristics of the human comorbid pathology, including hypertension and hyperglycemia. Although STZ lowered blood pressure in SHR, the animals remained hypertensive as compared to the Wistar controls. Plasma levels of triacylglycerols, cholesterol and HDL were increased, while markers of liver damage such as ALT, AST, were increased and albumin was decreased. Plasma BChE activities were similar in Wistar and SHR. In SHR+DM, plasma BChE activity was increased by 43 %. Interestingly, liver BChE activity and relative mRNA expression were decreased by 60 % in SHR and SHR+DM. While plasma BChE activity is often used as a clinical marker of liver injury, our results suggest that it may not be a reliable indicator. Key words Butyrylcholinesterase " Streptozotocin " Spontaneously hypertensive rats " Diabetes mellitus " Liver damage.
- MeSH
- Biomarkers blood MeSH
- Butyrylcholinesterase * blood MeSH
- Diabetes Mellitus, Type 1 * blood enzymology MeSH
- Diabetes Mellitus, Experimental * blood enzymology complications MeSH
- Hypertension * blood enzymology MeSH
- Liver * enzymology physiopathology MeSH
- Rats MeSH
- Rats, Inbred SHR MeSH
- Rats, Wistar MeSH
- Streptozocin MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Butyrylcholinesterase * MeSH
- Streptozocin MeSH
Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as "organ-on-chip," that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.
- Keywords
- animal model, diabetes mellitus, history, organ-on-chip,
- Publication type
- Journal Article MeSH
- Review MeSH
Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.
- MeSH
- Cytoprotection drug effects MeSH
- Diabetes Mellitus, Experimental drug therapy MeSH
- Flavanones isolation & purification pharmacology MeSH
- Mice MeSH
- Fruit chemistry MeSH
- Free Radical Scavengers isolation & purification pharmacology MeSH
- Scrophulariaceae chemistry MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Flavanones MeSH
- Free Radical Scavengers MeSH