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RISS 인기검색어
- 검색키워드
- 저자 : Luciano Saso (검색결과 3 건)
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Stabilization of Rat Serum Proteins Following Oral Administration of Fish Oil
Saso, Luciano,Valentini, Giovanni,Mattei, Eleonora,Panzironi, Claudio,Casini, Maria Luisa,Grippa, Eleonora,Silvestrini, Bruno The Pharmaceutical Society of Korea 1999 Archives of Pharmacal Research Vol.22 No.5
The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated buy a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate the in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at $70^{\circ}C$ for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.
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Reversal of multidrug resistance in cancer cells by novel asymmetrical 1,4-dihydropyridines
Omidreza Firuzi,Katayoun Javidnia,Elham Mansourabadi,Luciano Saso,Ahmad Reza Mehdipour,Ramin Miri 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.11
Multidrug resistance (MDR) is an importantobstacle that limits the efficacy of chemotherapy in manytypes of cancer. In this study, 14 novel asymmetrical DHPspossessing pyridyl alkyl carboxylate substitutions at C3 andalkyl carboxylate groups at C5 in addition to a nitroimidazoleor nitrophenyl moiety at C4 position were synthesized. Calciumchannel blocking (CCB) activity was measured inguinea pig ileal longitudinal smooth muscle. Cytotoxicitywas tested on 4 human cancer cell lines, while MDR reversalcapacity was examined on P-glycoprotein overexpressingdoxorubicin resistant MES-SA-DX5 and compared withnon-resistant MES-SA cells. Compounds showed differentCCB (IC50: 29.3 nM–4.75 lM) and cytotoxic activities(IC50: 6.4 to more than 100 lM). Several compounds havingnitrophenyl moiety at C4, could significantly reverse resistanceto doxorubicin at 0.5 and 1 lM. The most active oneswere 7e and 7g containing ethyl carboxylate and isopropylcarboxylate at C5, respectively. CCB activity, which isconsidered an undesirable effect for these agents, of 7e and7g were 33 and 20 times lower than nifedipine, respectively. In conclusion, the newly synthesized asymmetrical DHPcompounds showed promising MDR reversal and antitumoralactivities with low CCB effects and could be of therapeuticvalue in drug resistant cancer.
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( Sagar Verma ),( Priyanka Singh ),( Shiffali Khurana ),( Nirmal Kumar Ganguly ),( Ritushree Kukreti ),( Luciano Saso ),( Devinder Singh Rana ),( Vibha Taneja ),( Vinant Bhargava ) 대한신장학회 2021 Kidney Research and Clinical Practice Vol.40 No.2
Moderate levels of endogenous reactive oxygen species (ROS) are important for various cellular activities, but high levels lead to toxic ity and are associated with various diseases. Levels of ROS are maintained as a balance between oxidants and antioxidants. Accu mulating data suggest that oxidative stress is a major factor in deterioration of renal function. In this review, we highlight the possible mechanism by which oxidative stress can lead to chronic kidney disease (CKD). This review also describes therapies that counter the effect of oxidative stress in CKD patients. Numerous factors such as upregulation of genes involved in oxidative phosphorylation and ROS generation, chronic inflammation, vitamin D deficiency, and a compromised antioxidant defense mechanism system cause pro gressive detrimental effects on renal function that eventually lead to loss of kidney function. Patients with renal dysfunction are highly susceptible to oxidative stress, as risk factors such as diabetes, renal hypertension, dietary restrictions, hemodialysis, and old age predispose them to increased levels of ROS. Biomolecular adducts (DNA, proteins, and lipids) formed due to reaction with ROS can be used to determine oxidative stress levels. Based on the strong correlation between oxidative stress and CKD, reversal of oxidative stress is being explored as a major therapeutic option. Xanthine oxidase inhibitors, dietary antioxidants, and other agents that scav enge free radicals are gaining interest as treatment modalities in CKD patients.
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