Projects
Name
Effect of sitagliptin on cisplatin acute and sub chronic nephrotoxicity in rats
University
Sultan Qaboos University
Domain
Pharmacology
Departement
Department of Pharmacology, College of Medicine, Sultan Qaboos University, Al-Khoud, Oman.
Head
Dr. Yousuf Al-Suleimani
Tutor
Prof. Badreldin H. Ali
Languages
English
Duration
4 weeks
Availability
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No Yes Yes No No No No
Type of Research Project
- Basic science
What is the background of the project?
sitagliptin is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. The drug works to competitively inhibit a protein/enzyme, dipeptidyl peptidase 4 (DPP-4), that results in an increased number of active incretins (Glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]), reduced amount of release of glucagon (diminishes its release) and increased release of insulin. Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion. We aim in testing whether sitagliptin would affect the acute and sub chronic nephrotoxicity of the anti-cancer drug cisplatin in rats. several physiological, biochemical, histopathological and immunohistochemical methods would be used: 1.Animals: 24 rats were randomly divided into four equal groups and treated for four consecutive weeks. The first group received a normal diet without treatment until the end of the study (control group). The second group was switched to a powder diet containing adenine (0.75%, w/w, in feed). The third group was given normal food and GA (SUPERGUMTM EM 10) in the drinking water at a concentration of 15%, weight/volume. The fourth group was given adenine in the feed as in group two, plus GA in drinking water at a concentration of 15%, weight/volume. During the treatment period, the rats were weighed weekly and one day before the last day of treatment were placed individually in metabolic cages to collect the urine voided in the last 24 h. 2. Hematological methods In the blood collected in heparinized tubes erythrocyte count (EC), hemoglobin (Hb) concentration and hematocrit (Packed cell volume, PCV) were analyzed using automated methods (COBAS MICROS, Roche, Palo Alto, CA, USA). 3. Biochemical methods The concentrations of creatinine and urea, as well as that of iron (Fe), ferritin (F), transferrin (Tf) and L-γ-glutamyl transferase (GGT) in serum were measured 4.Histopathological methods The kidneys were fixed in 10% neutral-buffered formalin, dehydrated in increasing concentrations of ethyl alcohol, cleared with xylene and embedded in paraffin. Three micrometer sections were prepared from kidney paraffin blocks and stained with hematoxylin and eosin (H & E). The microscopic scoring of the kidney sections was carried out in a blinded fashion by a pathologist who was unaware of the treatment groups
What is the aim of the project?
To find out if sitagliptin would mitigate cisplatin nephrotoxicity
What techniques and methods are used?
several physiological, biochemical, histopathological and immunohistochemical methods would be used. 1.Animals: 24 rats were randomly divided into four equal groups and treated for four consecutive weeks. The first group received a normal diet without treatment until the end of the study (control group). The second group was switched to a powder diet containing adenine (0.75%, w/w, in feed). The third group was given normal food and GA (SUPERGUMTM EM 10) in the drinking water at a concentration of 15%, weight/volume. The fourth group was given adenine in the feed as in group two, plus GA in drinking water at a concentration of 15%, weight/volume. During the treatment period, the rats were weighed weekly and one day before the last day of treatment were placed individually in metabolic cages to collect the urine voided in the last 24 h. 2. Hematological methods In the blood collected in heparinized tubes erythrocyte count (EC), hemoglobin (Hb) concentration and hematocrit (Packed cell volume, PCV) were analyzed using automated methods (COBAS MICROS, Roche, Palo Alto, CA, USA). 3. Biochemical methods The concentrations of creatinine and urea, as well as that of iron (Fe), ferritin (F), transferrin (Tf) and L-γ-glutamyl transferase (GGT) in serum were measured 4.Histopathological methods The kidneys were fixed in 10% neutral-buffered formalin, dehydrated in increasing concentrations of ethyl alcohol, cleared with xylene and embedded in paraffin. Three micrometer sections were prepared from kidney paraffin blocks and stained with hematoxylin and eosin (H & E). The microscopic scoring of the kidney sections was carried out in a blinded fashion by a pathologist who was unaware of the treatment groups
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
1. The student will first be trained on lab animal handling; the student will be taught how to administer drugs and collect blood samples from rats and mice In the lab the student will learn how to perform and read spectrophotometry they will also be taught and are excpect to work on Enzyme-linked immune sorbent assay (ELISA) technique and the use of autoanalyzer. 2. Students will be recording the findings, analyzing the data and comparing them with previously recorded data.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
no
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
-
Are there any legal limitations in the student’s involvement
Yes
We do not hold any responsibility if the students breach the rules of the laboratory and animal house and as conscience it compromises their safety.
Hours
6
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
Articles
- Ali; B. H. et al (2015). Gum acacia mitigates genetic damage in adenine-induces chronic renal failure. Euro. J. Clinical Investigations; 45 (12); 1221-1227.