الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 165 |  |  |
| | | from | 165 | | |
Abstract
The acute lung damage is a life-threatening pulmonary condition. Among lung illnesses, it is one of the most prevalent. More than 4% of all hospital admissions are due to ALI/ARDS, and 10% of all ICU hospitalizations are due to these conditions. The major problem with ALI is the diffuse alveolar damage, the production of lung edoema, the neutrophil-mediated inflammation, and the ventilation-perfusion mismatch, all of which reduce pulmonary compliance and lead to significant hypoxemia. To test the efficacy of cilostazol and ketotifen in LPS-induced ALI, we used a previously validated rat model of the disease. In the present investigation, we looked at whether ketotifen and cilostazol may prevent LPS-induced ALI.
Sixty-four albino Wistar males of average weight were used in this investigation (250-300g). The rats were split up into many different groups (n=5-8): Patients in the control group had intratracheal saline injected once after 14 days of receiving saline as a carrier. The ketotifen group received oral ketotifen (1mg/kg/day) for 14 days straight, followed by a single intratracheal saline injection on day 5. The cilostazol group took the drug orally (20mg/kg/day) for 14 days, whereas the saline group had a single intratracheal injection on day 5. In the ketotifen plus cilostazol group, rats were given the same dosages of ketotifen and cilostazol for 14 days in a row, followed by a single injection of intratracheal saline on day 5. In the LPS group, patients were given oral normal saline for 14 days in a row, and then on day 5, they were injected with a single dosage of intratracheal E-coli LPS 5mg/kg diluted in 0.9% saline. Rats were split into 3 groups and given either oral ketotifen, cilostazol, or combination ketotifen + cilostazol in the dosages listed above for 14 days straight before being challenged with a single dose of intratracheal LPS on day 5.
Total protein and TLC levels were measured in the BALF that was collected at the conclusion of the experiment. In addition to histopathological scoring, the W/D ratio, MDA, NO, SOD, TAC, caspase 3, cAMP, cGMP, MPO, histamine, ACE2, Ang (1-7), p38 MAPK, NF-B, and IL6 were measured in the lung tissue that was collected.
The current investigation found that exposure to LPS significantly exacerbated histological lung damage, as seen by elevated levels of lung W/D ratio, BALF total protein and TLC, MDA, NO, caspase 3, MPO, histamine, p38 MAPK, NF- B, and IL6 in the LPS group. Nevertheless, it resulted in a reduction in the concentrations of SOD, TAC, cAMP, cGMP, ACE2, and Ang (1-7).
Protective effects of ketotifen and cilostazol on the lung were seen in the form of a reduction in inflammatory biomarkers (decreased P38 MAPK, NF-kB, IL6, MPO, histamine, BALF total protein, and TLC) and a subsequent improvement in lung histology as compared to the LPS non-treated group. Accompanying this protective effect was a reduction in apoptotic marker caspase-3 and a restoration of the oxidative stress/antioxidant balance (decreased level of MDA, NO and elevated both SOD and TAC). As a result, cAMP, cGMP, ACE2 density, and Ang (1-7) were all elevated.
The antioxidant, anti-inflammatory, antiapoptotic, and ACE2/Ang (1-7) up-regulatory actions of ketotifen and cilostaol, respectively, were indicative of their protective activities.
The results of the current investigation are as follows: First, LPS-induced ALI, which includes inflammation, oxidative damage, and apoptosis. Two, both ketotifen and cilostazol have lung-protective properties. Ketotifen and cilostazol’s protective effects on LPS-induced ALI were ascribed, at least in part, to their anti-inflammatory, antioxidant, antiapoptotic, and ACE2/Ang (1-7) up-regulatory action.
In conclusion, the medicines utilised had a protective effect against LPS-induced ALI via a number of distinct molecular pathways. These findings suggest that ketotifen and cilostazol may be useful in the treatment of ALI/ARDS and the inflammatory symptoms that accompany these conditions in the future.