Cardiovascular Physiology - Regulation of Cardiac Pumping
2 evaluation of vitamin c as a potential anti tuberculosis
1. Evaluation of Vitamin C as a potential anti-
tuberculosis drug in Guinea pig model of tuberculosis
Misbah Un Nisa
12056100018
2. Tuberculosis; definition and symptoms
Tuberculosis is a second largest infectious disease
caused by Mycobacterium tuberculosis that usually
effects lungs although other organs may also be
involved.
The symptoms of active disease include mild fever,
headache, chills, night sweats, fatigue, coughing up
blood, chest pain etc
Transmission usually takes place through the
airborne spread of droplet nuclei produced by
patients with infectious TB.
3. TB as global health threat
• In 2012, there were an estimated 8.6 million cases of
TB
• 1.3 million people died from the disease
• India accounts for the 26% of total cases
• Largest no. of incident cases of TB in 2012 were
reported from India & the largest increase in MDR TB
cases between 2011 & 2012 were reported from India
• Leading killer of people living with HIV/AIDS
Global TB report 2013, WHO
4. Combating strategies for TB
A. Vaccines:
• Currently only available vaccine, BCG, is in use for non pulmonary TB
B. Therapeautic strategy:
• The currently recommended treatment for new cases of drug-susceptible
TB is a regimen with two months of four first line drugs: isoniazid, rifampin,
pyrazinamide & ethambutol, followed by continuation phase for four to
eight months with isoniazid & rifampin.
• For patients with MDR-TB/XDR TB, second line drugs which include
injectable amino glycosides capreomycin, kanamycin and amikacin; and
fluoroquinone antibiotics are used
• For patients with TDR TB no drugs are available as yet
5. What is MDR, XDR, TDR-TB?
• A form of disease caused by bacilli resistant to at least
isoniazid & rifampin is called MDR TB
• XDR TB is a form of disease in which MDR TB is
compounded by additional resistance to the most
powerful second line drugs : fluoroquinolones and at
least one of the injectable drugs amaikacin,
kanamycin and capreomycin
• TDR TB is the form of TB in which the bacilli are
resistant to all the available anti-TB drugs
6. Is there a need for new drugs?
• The anti-TB drugs currently used in first-line treatments are
around 50 years old.
• The fact that 8.6 million new TB cases and 1.3 million TB deaths
were reported in 2012 clearly suggests the urgent need of new
strategies for TB treatment
• There is a demand for discovery of new drug regimens which
should:
1. Shorten treatment duration
2. Target MDR-TB & XDR-TB strains
3. Simplify treatment
4. Be co-administered safely with HIV medications
7. Origin of the project
• In a recent study by Catherine et al Vit C has shown
potent in vitro activity against both drug
susceptible and drug resistant strains of M.
tuberculosis
• The study we plan to undertake is to evaluate Vit C
in preclinical animal models as anti-TB drug
8. Exploring Vitamin C as a potent
anti-tuberculosis drug
• Recent research on vitamin C has shown it to sterilize cultures
of drug susceptible and drug resistant strains of M.Tuberculosis.
• Vit C is non mutagenic, non toxic & one of the essential
components of body
• Vitamin C drives Fenton Reaction and results in production of
hydroxyl radicals which cause DNA damage and thus cell death.
• Bactericidal activity of vitamin C is dependent on
– High ferrous ion levels.
– Production of reactive oxygen species.
(Catherine et al, 2013)
11. Hypothesis
Since Vit C has shown potent in vitro activity
against both drug susceptible and drug resistant
strains of M. tuberculosis, therefore we
hypothesize that Vit C bears a great potential for TB
treatment keeping in view bioavailability of Vit C
upon oral dosing in humans and other animals.
12. Specific objectives
1. To evaluate Vit C in vitro against drug susceptible, MDR and
XDR strains of M.tb with or without existing anti-TB drugs
2. To determine if activity of Vit C is driven by concentration
or time or both under in vitro conditions
3. To evaluate pharmacokinetics of Vit C in guinea pigs over a
range of doses
4. To evaluate mono therapy of vit C against acute as well as
chronic models of guinea pig TB
5. To evaluate vit C in combination with existing anti-TB drugs
in guinea pig model of TB
15. PK studies in Guinea pigs
Inject guinea pigs with
different doses of vit C
Draw blood at different
time points
HPLC analysis for PK of
vit C
16. • Infect groups of Guinea pigs with 105CFU/ml & 108 CFU/ml resp.
• Sacrifice after a day for determination of basal bacterial load
• Start treatment after 28 / 14 days resp. with different doses of
Vit C based on MIC/PK studies for 4 weeks
• Sacrifice at day 28/14 resp. for CFU enumeration
• Repeat Vit C groups with different combinations of drugs
Vit C evaluation in Guinea pigs
17. Significance of the project
This study enlightens the possible benefits of
adding vit C to anti-TB regimen & suggests that the
development of drugs that generate high oxidative
burst could be of great use in TB treatment.
18. Total budget estimate
Item Budget in Lakhs (INR) Total INR in
lakhs
Ist year 2nd year 3rd year
A RECURRING
Salaries 3.12 3.12 3.12 9.36
Consumables 5.0 5.0 5.0 15.0
Travel 0.5 0.5 0.5 1.5
Overhead charges @
10%
0.862 0.862 0.862 2.586
SUBTOTAL 9.482 9.482 9.482 28.446
B NON RECURRING
Equipment (BSL-2-
cabinet,centifuge,spec
trophotometer etc)
37.0 37.0
GRAND TOTAL 65.446
