EFFICACY OF TEST FORMULATIONS IN RAT MODEL OF VANCOMYCIN-INDUCED NEPHROTOXICITY

 

EFFICACY OF TEST FORMULATIONS IN RAT MODEL OF VANCOMYCIN-INDUCED NEPHROTOXICITY

1.0  TEST SYSTEM DETAILS:

Species                   : Rattus norvegicus (Rats)

Age                        : 7-8 weeks

Sex                         : Male/Female

No. of animals        : 8 /Group

Total animals          : 48

 

2.0   ALLOCATION OF GROUPS:

 

Group No.	Group Description	Disease Induction agent administered	Treatment administered	Dose Volume and Route
G1	Normal Control	Water for injection b.i.d. × 10 days by intraperitoneal route (i.p.)	0.25% Na-CMC, p.o., q.d.	5 ml/kg, p.o.
G2	Disease Control	Vancomycin – 200 mg/kg, i.p., b.i.d. × 10 days	0.25% Na-CMC, p.o., q.d.
G3	Reference Control		Melatonin 20 mg/kg, q.d. in 0.25% Na-CMC
G4	Treated with low dose of TF		TF-X1 mg/kg, q.d.,  in 0.25% Na-CMC
G5	Treated with intermediate dose of TF		TF-X2 mg/kg,    q.d., in 0.25% Na-CMC
G6	Treated with high dose of TF		TF-X3 mg/kg,   q.d., in 0.25% Na-CMC

Abbreviations: Na-CMC-Sodium Carboxymethyl Cellulose, p.o.-per os. q.d.: quaque die; bid: bis in die. X1, X2, X3, X4 are defined as the incremental doses of the Test formulations. The dose range will be from 10 mg/kg to 1000 mg/kg, q.d.

 

3.0  METHOD:

·       Healthy animals will be selected, randomized based on body weight and allocated into 6, different groups consisting of 8 animals each.

·       Normal control group (G1) will be injected water for injection by intraperitoneal route, twice a day for 10 days. Animals allocated to G2 – G6 will be administered vancomycin (200 mg/kg, i.p.) dissolved in water for injection, twice a day for 10 consecutive days.

·       Animals of the Group G1 will serve as sham-control and administered 0.25% Na-CMC, p.o., b.i.d.

·       Disease control animals (assigned to group G2)  will receive 0.25% Na-CMC, p.o., b.i.d.

·       Animals of group G3 will be treated with reference drug Melatonin at the dose of 20 mg/kg, p.o., q.d.

·       Animals of group G4-G6 will be treated with TF at different dose levels ranging from 10-1000 mg/kg, b.i.d.

·       Compound administration will be initiated 5 days prior to and 10 days concurrently with vancomycin administration.

·       Twelve hours after the last vancomycin injection, animals will be placed in metabolic cages for urine collection for a total duration of 24 hours. Subsequently, they will be sacrificed under overdose of thiopentone anesthesia. After suitable anesthesia but before the animal dies, blood will be collected from the retro-orbital plexus for the estimation of biochemical parameters. Immediately after the animal dies, the kidneys will be weighed and the left kidney will be fixed in 10% neutral buffered formalin for histopathological whereas the right kidney will be stored at -80°C for the ensuing biochemical and molecular evaluations.

 

4.0  END POINT PARAMETER(S):

·       Kidney weight

·       Urinary biochemistry parameters: N-acetyl-ß-D glucosaminidase and Kidney Injury Marker - 1

·       Serum Biochemical Parameters: Creatinine, Blood Urea Nitrogen

·       Oxidative stress parameters in the kidney: Reduced and oxidative glutathione, malonaldehyde, nitric oxide, catalase superoxide dismutase and glutathione peroxidase.

·       Caspase 3 and 9 in kidney tissue

·       qPCR in kidney tissue: NF-κB, iNOS and TNF-α

·       Serum cytokines: TNF-α, IL-1β and IL-6

·       Histological Analysis of kidney tissue (H&E).

 

5.0  REFERENCE(S):

1.       Celik, I., Cihangiroglu, M., Ilhan, N., Akpolat, N. & Akbulut, H. H. Protective Effects of Different Antioxidants and Amrinone on Vancomycin-Induced Nephrotoxicity. 325–332 (2005).

2.        Basarslan, F. et al. Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum. Exp. Toxicol. 31, 726–733 (2012).

3.        Elyasi, S., Khalili, H., Dashti-Khavidaki, S. & Mohammadpour, A. Vancomycin-induced nephrotoxicity: Mechanism, incidence, risk factors and special populations. A literature review. Eur. J. Clin. Pharmacol. 68, 1243–1255 (2012).

4.        Guzel, S. et al. Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats. Drug Chem. Toxicol. 0, 1–7 (2019).

                                   

                                  END OF DOCUMENT

You may like to read theses links:   

1. List of All SOPs and Documents for In-vivo Laboratory

2. List of All SOPs and Documents for Study Protocol

3. List of Pharmacological Study Models with details about disease Inducing agent, Standard or Reference Drug and related parameters.

4.List of OECD Guidelines or Toxicological Studies

5.List of Pharmacopeial Test or Quality Control Test or Batch Testing Parameters (In-vivo)

 

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