الفهرس 
Introduction and Aim of workOnly 14 pages are availabe for public view
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Abstract
Cancer is considered as an important and common cause for the morbidity and mortality
in the world. Chemotherapy is the use of substances such as chemicals or medications to eradicate
cancer cells through a local or systemic effect. Even in locations far from the primary tumor’s
origin, chemotherapy slows the development and kills cancer cells. However, it lacks the ability
to discriminate between cancer and healthy cells, and it also destroys the body’s other rapidly
proliferating cells. There are a variety of classes of anticancer drugs depending on their mechanism
of action, and they classified into: alkylating agents which damage DNA, antibiotics that interfere
with the enzymes involved in DNA replication, mitotic inhibitors that inhibit mitosis,
topoisomerase inhibitors that inhibit either topoisomerase I or II, anti-metabolites that replace the
normal building blocks of RNA and DNA and corticosteroids which are involving in the therapy
of the cancer and to attenuate the side effect of the other drugs. Cisplatin is an effective
chemotherapy belonging to the alkylating agent.
Decades ago, natural products were used for many different therapeutic purposes due to
their proven protective effect against several disease conditions. Now, many plants’ natural
products are under investigation to be used with anticancer agents to counteract their toxic side
effect -depending on their natural antitoxic effect- and hence improve patients’ compliance.
K which is a natural product with proved protective antioxidant effect, is now investigated
for its ability to counter act the adverse toxic effects caused by the chemotherapeutic agent
cisplatin. Our in vitro results on both normal and cancer lung cell lines proved the safety effect of
K. Our in vivo study results on lung and kidney tissues proved the safety and protective effect of
K when used alone, in a dose dependent manner with highest effect achieved with a dose 1mg/kg,
and the protective effect of K when administered with cisplatin.
Concerning histological results of lung tissues, lung histological findings were in
consistance with the results of lipid peroxidation (MDA), oxidative stress status, pulmonary
antioxidant status (SOD and GSH), and DNA damage assay. Histopathological study stated a
disruption of the alveoli membranes, vasodilation, and blood congestion of vascular capillary with the cisplatin. This disruption in the tissue structure might illustrate the effect of oxidative stress
stimulated by cisplatin to harmly affect lung tissue. K alone showed no damage effect or alteration
confirming the safety of K.
In lung tissues, the antioxidant effect was shown by significant elevation in SOD and GSH
content. When administered with cisplatin, K can restore the oxidative effect of cisplatin and
significantly elevate the reduced GSH level. This antioxidant effect is similar to the effect achieved
by vitamin C. The ability of K to reduce MDA level in lung tissues demonstrated its protective
action against oxidative stress in addition to lipid peroxidation. When administered with cisplatin,
K can restore the oxidative stress and lipid peroxidation caused by cisplatin and significantly
reduce the elevated level of MDA again. This ability to restore oxidative stress and lipid
peroxidation effect is similar to the effect achieved by vitamin C.
The protective ability of K against DNA oxidative damage in lung tissues was proved by
the significant decrease achieved in 8-OHDG level. When administered with cisplatin, K can
restore the DNA oxidative damage caused by cisplatin and significantly decrease the elevated level
of 8-OHDG. This protective ability of K against DNA oxidative damage is similar to the protective
effect achieved by vitamin C.
The antiapoptotic effect of K in lung tissues was estimated through measurement of cleaved
caspase3, BAX and BCl2 proteins. K has an antiapoptotic effect which proved by its ability to
decrease level of cleaved caspase3 and proapaptotic protein BAX. When administered with
cisplatin, K can restore the apoptotic effect caused by cisplatin and decrease the elevated level of
cleaved caspase3 and BAX proteins. Also, K restored the decreased level of antiapoptotic protein
BCl2 caused by cisplatin and elevated it again. Interestingly, this antiapoptotic effect of K and
ability to restore apoptosis effect of cisplatin by decrease BAX and increase BCl2 level is better
than the effect achieved by vitamin C in lung tissues.
Confirming the protective effect of K on kidney functions, serum urea and creatinine levels
were estimated. Again, K proved its protective action on kidney function when administrated with
cisplatin, by its ability to significantly decrease the elevated levels of serum urea and creatinine
achieved by cisplatin administration.