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. 2020 Feb 5;12(2):414. doi: 10.3390/nu12020414

Table 3.

Characteristics of animal studies related to myocardial infarction included in the review.

Study Disease/
Condition		 Study Type/
SQ Source		 Sample/
Population		 Methodology Results
(SQ and CVD only)		 Comments/Outcomes
Study 1
Farvin et al. 2004 [57]		 Myocardial infarction Animal study
 
Isolated from fresh shark liver		 Wistar strain male albino rats (100–120 g)
 
Divided into four groups
(six rats per group)		 Following 7-day acclimatization, the rats were divided according to groups, were fed on a standard diet with added oils for 45 days, and were injected with saline or isoproterenol for 2 days. Isoproterenol was used to induce myocardial infarction in rats.
 
Group I (control):
2% coconut oil and injected with saline
Group II (control):
2% SQ and injected with saline
Group III:
2% Coconut oil and injected with isoproterenol
 
Group IV:
2% SQ and injected with isoproterenol
At the end of the experiment
(24 h after last isoproterenol injection), the rats were sacrificed for blood collection and heart excision.
Measurement involved
a) antioxidant enzymes
GPx and GST, and
b) anti-peroxidative
enzymes
CAT and SOD.		 The prior treatment with SQ had significantly increased the activities of antioxidant enzymes (GPx and GST) and anti-peroxidative enzymes (CAT and SOD) in the heart tissue of group IV as compared to group III isoproterenol-induced myocardial infarcted rats (p < 0.001).
 
The normal rats receiving SQ alone (group II) did not show any significant change in comparison to the control (group I).		 SQ supplementation possesses a cardioprotective effect due to their antioxidant property.
 
No adverse effect following a low dose of SQ supplementation (at 2%)
Study 2
Farvin et al. 2005 [58]		 Myocardial infarction Animal study
 
Shark liver oil of Centrophorus sp. caught in Andaman waters		 Wistar male albino rats (100–120 g)
 
Divided into four groups (six rats per group)		 All rats were fed on a standard diet with added oils for 45 days and were injected with saline or isoproterenol for 2 days according to the groups. Isoproterenol was used to induce myocardial infarction in rats.
 
Group I (control):
2% coconut oil and injected with saline
Group II (control):
2% SQ and injected with saline
Group III:
2% coconut oil and injected with isoproterenol
Group IV:
2% SQ and injected with isoproterenol
 
At the end of the experiment,
(24 h after last isoproterenol injection), the rats were sacrificed for blood collection and heart excision.
 
Measurement involved
a) diagnostic marker enzymes,
b) membrane-bound ATPase (Na+, K+ ATPase, and Ca2+ ATPase) activities and mineral status (sodium, potassium, and calcium), and
c) lipid peroxidation and GSH		 The pretreatment of 2% SQ in the diet had significantly reduced the release of diagnostic marker enzymes (ALT, AST, LDH, and CPK) into the systemic circulation as compared to group III rats (p < 0.001).
 
The pretreatment of 2% SQ in the diet also had significantly counteracted the isoproterenol-induced lipid peroxidation and maintained the level of GSH at near normalcy in group IV rats as compared to group III animals (p < 0.001).
 
SQ supplementation exerted membrane-stabilizing action against isoproterenol-induced myocardial infarction by maintaining the activities of membrane-bound ATPase (Na+, K+ ATPase, and Ca2+ ATPase) activity in the heart tissue and the mineral status (sodium, potassium, and calcium) in plasma and heart tissue at near-normal levels.		 The cardioprotective effect of SQ might be contributed by the antioxidant property and membrane-stabilizing action.
Study 3
Farvin et al. 2006 [59]		 Myocardial infarction Animal study
 
Isolated from fresh shark liver		 Male Wistar strain albino rats
(120–150 g)
Divided into four groups (six rats per group)		 All animals were fed on a standard diet with added oils for 45 days and injected with saline/isoproterenol for 2 days according to the groups. Isoproterenol was used to induce myocardial infarction (MI) in rats.
 
Group I (control):
2% coconut oil and injected with saline
Group II (control):
2% SQ and injected with saline
Group III:
2% coconut oil and injected with isoproterenol
Group IV:
2% SQ and injected with isoproterenol
 
At the end of the experiment,
(24 h after last isoproterenol injection), the rats were sacrificed for blood collection and heart tissue excision
Measurement involved
  • a)

    lipid parameters in plasma cholesterol, triglycerides, free fatty acids, phospholipids, LDL-C, and HDL-C;

  • b)

    lipid parameters in heart tissue cholesterol, triglycerides, free fatty acids, and phospholipids; and

  • c)

    lipid peroxides in plasma and heart tissue.

 For normal rats (group I vs group II), SQ supplementation to the normal rats (group II) had significantly increased plasma HDL-C levels compared to the group I normal control rats (p < 0.01).
 
Plasma lipid peroxidation in group II (normal squalene-fed rats) showed a slight decline as compared with group I normal control animals (p < 0.05).
 
For MI-induced rats (group III vs group IV), both plasma and heart tissue levels of cholesterol, TG, free fatty acids, phospholipids, and LDL-C in MI-induced rats in group IV were significantly decreased in comparison to that of group III (p < 0.001). In contrast, the HDL-C level in group IV had also significantly increased compared to Group III.
 
Both plasma and heart tissue lipid peroxidation in group IV MI-squalene fed were significantly decreased when compared with group III MI-control rats (p < 0.001).		 The pre-administration of 2% SQ for 45 days prevents the symptoms of isoprenaline-induced myocardial infarction in rats.
 
The cardioprotective effect of SQ might be related to its ability to inhibit lipid accumulation by
  • i)

    hypolipidemic property and

  • ii)

    free-radical scavenging ability against isoprenaline-induced lipid peroxidation.
Study 4
Farvin et al. 2007 [60]		 Myocardial infarction Animal study
 
Isolated from fresh shark liver		 Twenty-four Wistar strain male albino rats (120–150 g)
 
Divided into four groups of six rats per group		 All rats were fed on a standard diet with added oils for 45 days and were injected with saline or isoproterenol for 2 days according to the groups. Isoproterenol was used to induce myocardial infarction in rats.
Group I (control):
2% coconut oil and injected with saline
Group II (control):
2% SQ and injected with saline
Group III:
2% coconut oil and injected with isoproterenol
Group IV:
2% SQ and injected with isoproterenol
 
At the end of the experiment,
(24 h after last isoproterenol injection), the rats were sacrificed for blood collection and heart tissue excision.
Measurement involved
a) protein content,
b) hexose and hexosamine content,
c) lipid peroxidation in the presence of promoters (ascorbic acid, ferrous sulphate, and tert-butyl hydroperoxide), and
d) GSH		 The pretreatment of 2% SQ (group IV) had significantly decreased the level of protein, hexose, and hexosamine in both plasma and heart tissue (p < 0.05). The group had also significantly increased in the level of GSH and maintained it to near normalcy (p < 0.05).
 
In the presence of promoters (ascorbic acid, ferrous sulphate, and tert-butyl hydroperoxide) in the heart tissue, group IV (MI-SQ) had significantly decreased (p < 0.05) lipid peroxidation levels when compared to the control group (group III MI-control rats).
 
The normal rats receiving squalene (group II) showed a significant change (p < 0.05) for the level of protein and hexose in the heart tissue when compared with normal control rats (group I).		 The pretreatment of SQ might exert cardioprotective effects by preventing isoprenaline-induced necrotic damage to the myocardial cell membrane by its membrane-stabilizing and antioxidant properties.
Study 5 Dhandapani et al. 2007 [61] Myocardial infarction Animal study
 
Shark liver oil Centrophorus sp.
caught in the Andaman waters		 Forty-eight Wistar strain male albino rats
(120–150 g)
 
Divided into four groups of 12 rats per group		 The rats were fed on
commercial feed added with the following oils at a 2% level for 60 days:
group 1: coconut oil,
group 2: SQ,
group 3: PUFA concentrate, and
group 4: SQ + PUFA concentrate.
After 60 days, each group was further subdivided into eight groups of six rats per group:
1) groups 1a and 1b; 2a and 2b; 3a and 3b; and 4a and 4b,
were i.p. injected with only saline for two days (control animals) and
 
2) groups 1b, 2b, 3b, and 4b rats
were i.p. injected with isoprenaline for two days to induce myocardial infarction.
 
At the end of the experimental period, the rats were sacrificed for blood collection and heart excision.
Measurement involved
1) diagnostic marker enzymes (ALT, AST, LDH, and CPK) and
2) lipid peroxides (LPO), reduced glutathione (GSH), and antioxidant enzymes.		 Pre-supplementation with SQ alone (Group 2b) had significantly reduced the release of these enzymes (ALT, AST, LDH, and CPK) from the myocardium into the systemic circulation as compared to group 1b isoprenaline-administered rats (p < 0.001).
 
Pre-supplementation with SQ alone (group 2b) had significantly reduced the LPO (p < 0.001) and significantly elevated GSH and antioxidant enzymes when compared to group 1b isoprenaline-administered rats (p < 0.001).
 
Th normal SQ-fed rats (group 2a) showed no significant changes when compared to normal control rats (group 1a) rats.		 Supplementation of SQ significantly counteracts the isoprenaline-induced elevations in the levels of diagnostic marker enzymes and LPO and is able to maintain the level of antioxidant enzymes at near normalcy.
 
The administration of SQ may exert significant cardioprotection against isoprenaline intoxication.
Study 6
Farvin et al. 2009 [62]		 Myocardial infarction Animal study
 
Shark liver oil Centrophorus sp. caught in the Andaman waters		 Male Wistar strain albino rats
(120–150 g)
 
Divided into four groups of six rats per group.		 All animals were fed on a standard diet with added oils for 45 days and injected with saline/isoproterenol for 2 days according to the groups. Isoproterenol was used to induce myocardial infarction in rats.
 
Group I (control):
2% coconut oil and injected with saline
Group II (control):
2% SQ and injected with saline
Group III:
2% coconut oil and injected with isoproterenol
 
Group IV:
2% SQ and injected with isoproterenol
At the end of the experimental period (24 h after the last isoproterenol injection), the animals were sacrificed for blood collection and heart tissue excision.
 
Measurement involved
1) ascorbic acid,
2) alpha tocopherol, and
3) endogenous squalene content.		 Prior administration of 2% SQ in the diet (group IV) significantly increased the endogenous antioxidants (vitamin C and vitamin E) compared to MI-control rats (group III) (p < 0.001).
 
The administration of 2% SQ in the diet also significantly restored the membrane-bound SQ content in the heart tissue compared to MI-control rats (group III) (p < 0.001).		 SQ supplementation potentially exerts a deleterious effect of isoprenaline-induced aberration in endogenous antioxidant vitamins in experimental rats.
 
SQ may exert cardioprotective effect via the ability to counteract free radicals by its antioxidant nature or membrane-stabilizing action.