Do all protein bound renal toxins exert physiological effects on cardiac cells?

P Iyngkaran, K L Tuck, J Ma, P Ho, S Lekawanvijit, A Kompa, B Wang, H Krum

Research output: Contribution to conferenceAbstract

Abstract

Background: The protein bound renal toxins (PBRT)indoxyl sulphate and homocysteine have known clinical and physiological cardiovascular effects. Several studies with other PBRT noted clinical cardiovascular associations, however direct physiological effects have not been investigated on cardiac cells.

AIM: To assess the direct effects of PBRT’s, Phenyl acetic acid (PAA),m/p-Cresol (MC/PC) and their main circulating in vivo metabolitem/p-Cresylsulphate (MCS/PCS) on neonatal cardiac myocyte (NCM) hypertrophy and fibroblast (NCF) collagen synthesis.

Materials and method: MC/PC were reacted with sulfur trioxide N,N-dimethylformamide complex to give the corresponding sulphates (PCS/MCS) as the sodium salts in moderate yields. Purity was confirmed by proton NMR spectroscopy and MS. NCM and NCF were iso-lated by enzymatic digestion, cultured and pretreated with increasing doses of PBRT. NCF collagen synthesis and NCM hypertrophy were determined by 3H-proline and 3H-leucine incorporation. Cell viability was assessed with MTT assays.

Results: PC had minor inhibitory effect while PCS, MC, MCS, PAA, had no significant effect on NCF collagen synthesis and NCM hypertrophy at 100 μm (100μm PBRT vs Control: PC: 112.4±1.8, PCS: 118.9±9.2, MC:117.1±4.4, MCS: 104.6±7.6, PAA: 93.8±4.3; AllP> 0.05). With 100 nM Angiotensin II stimulation, 100μm PBRT also did not effect NCF collagen synthesis and NCM hypertrophy (100μm PBRT + 100 nM AngII vs Control: PC:87.5±5.8, PCS: 89.0±0.7%, MC: 94.2±4.8, MCS: 90.1±7.2,PAA: 87.6±4.9; all P> 0.05). Furthermore, PBRT’s tested did not affect NCF and NCM cell viability.

Conclusion: Despite these compounds being elevated in clinical settings (chronic renal failure) we were unable to demonstrate direct effects on NCF and NCM. The clinical effects of these compounds may occur via other mechanisms which are worthy of further investigation.
Original languageEnglish
PagesS250-S251
Number of pages2
DOIs
Publication statusPublished - 2009
EventCardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research, Australasian Section, Annual Scientific Meeting, 2009 - Sydney, Australia
Duration: 13 Aug 200916 Aug 2009

Conference

ConferenceCardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research, Australasian Section, Annual Scientific Meeting, 2009
CountryAustralia
CitySydney
Period13/08/0916/08/09

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